Updated on 2024/02/19

写真a

 
TAKASE Kenkichi
 
Organization
Faculty of Letters Professor
Other responsible organization
Psychology Course of Graduate School of Letters, Master's Program
Psychology Course of Graduate School of Letters, Doctoral Program
Profile

How do the biological, psychological, and social factors cause sex-specific abnormal behaviors in a specific development stage? This is the question that motivates the research in my laboratory, and I would like to provide the findings which lead to the development of intervention techniques for correcting sex-specific abnormal behaviors in a specific development stage. Moreover, I am also interested in the development of the methodology which expands the utility of animal models, since mice and rats are used in my research, as animal models for the study of human abnormal behaviors. Furthermore, our laboratory is promoting the collaboration between psychology and other disciplines to expand the research area of psychology.

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Degree

  • 博士(行動科学) ( 筑波大学 )

  • 修士(医学) ( 横浜市立大学 )

Education

  • 2004.3
     

    Yokohama City University   master course   completed

  • 2002.3
     

    Ritsumeikan University   others   graduated

Research History

  • 2023.8 - Now

    Aichi University

  • 2022.4 - Now

    Jichi Medical University

  • 2022.4 - Now

    Chuo University   Faculty of Letters Department of Humanities and Social Sciences   Professor

  • 2021.4 - Now

    The Open University of Japan

  • 2021.4 - Now

    Toho University

  • 2020.12 - Now

    National Institute of Science and Technology Policy

  • 2015.3 - Now

    公立大学法人 横浜市立大学   医学部 医学科 麻酔科学教室   客員教授(兼務)

  • 2012.4 - Now

    Yokohama City University   School of Medicine Medical Course

  • 2022.4 - 2022.9

    Hokkaido University   Graduate School of Life Science

  • 2021.10 - 2022.3

    Keio University   Faculty of Letters

  • 2017.6 - 2022.3

    Jichi Medical University   Professor

  • 2016.4 - 2022.3

    Jichi Medical University   Professor

  • 2014.8 - 2022.3

    Jichi Medical University   School of Medicine   Professor

  • 2020.4 - 2021.3

    Toho University

  • 2015.4 - 2021.3

    Jichi Medical University

  • 2020.3 - 2020.8

    Mitsubishi Research Institute, Inc.

  • 2019.8 - 2019.9

    公立大学法人 首都大学東京   大学院人間健康科学研究科 ヘルスプロモーション学域   非常勤講師(兼務)

  • 2018.1 - 2019.6

    国立特別支援教育総合研究所   特別支援教育専門研修 知的障害教育コース   非常勤講師(兼務)

  • 2013.8 - 2014.7

    Toho University   School of Medicine, Faculty of Medicine

  • 2013.4 - 2014.3

    公立大学法人 横浜市立大学   医学部 医学科 麻酔科学教室   客員研究員(兼務)

  • 2013.4 - 2014.3

    University of Tokyo Health Sciences

  • 2011.4 - 2013.7

    Toho University   School of Medicine, Faculty of Medicine   Assistant Professor

  • 2011.4 - 2012.3

    University of Human Arts and Sciences   Division of Human Sciences, Department of Human Sciences

  • 2008.4 - 2011.3

    Himeji Dokkyo University   Faculty of Pharmaceutical Sciences, Department of Pharmaceutical Health Care

  • 2005.4 - 2008.3

    公立大学法人 横浜市立大学   医学部 医学科 生理学教室   助手

  • 2006.4 - 2007.3

    Mejiro University   Faculty of Human and Social Sciences, Department of Psychological Counseling

  • 2004.4 - 2005.3

    Yokohama City University   School of Medicine Medical Course , Physiology   Research Assistant

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Professional Memberships

  • 日本心理学会

  • 日本発達心理学会

  • 日本赤ちゃん学会

  • 日本学生相談学会

  • 日本行動科学学会

  • 日本動物心理学会

  • 日本神経科学学会

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Research Interests

  • 生涯発達支援

  • sex difference

  • 孤立・孤独

  • development

  • developmental disorder

Research Areas

  • Humanities & Social Sciences / Clinical psychology

  • Humanities & Social Sciences / Educational psychology

  • Humanities & Social Sciences / Experimental psychology

Papers

  • Understanding Sensory-Motor Disorders in Autism Spectrum Disorders by Extending Hebbian Theory: Formation of a Rigid-Autonomous Phase Sequence Reviewed

    Eiichi Nojiri, Kenkichi Takase

    Perspectives on Psychological Science   2023.11

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    Autism spectrum disorder is a neuropsychiatric disorder characterized by persistent deficits in social communication and social interaction and restricted, repetitive patterns of behavior, interests, or activities. The symptoms invariably appear in early childhood and cause significant impairment in social, occupational, and other important functions. Various abnormalities in the genetic, neurological, and endocrine systems of patients with autism spectrum disorder have been reported as the etiology; however, no clear factor leading to the onset of the disease has been identified. Additionally, higher order cognitive dysfunctions, which are represented by a lack of theory of mind, sensorimotor disorders, and memory-related disorders (e.g., flashbacks), have been reported in recent years, but no theoretical framework has been proposed to explain these behavioral abnormalities. In this study, we extended Hebb’s biopsychology theory to provide a theoretical framework that comprehensively explains the various behavioral abnormalities observed in autism spectrum disorder. Specifically, we propose that a wide range of symptoms in autism spectrum disorder may be caused by the formation of a rigid-autonomous phase sequence (RAPS) in the brain. Using the RAPS formation theory, we propose a biopsychological mechanism that could be a target for the treatment of autism spectrum disorders.

    DOI: 10.1177/17456916231202674

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    Other Link: http://journals.sagepub.com/doi/full-xml/10.1177/17456916231202674

  • シチズン・サイエンスの成果をどうアウトプットするか Invited Reviewed

    髙瀨 堅吉

    情報の科学と技術   73 ( 11 )   507 - 513   2023.11

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    Authorship:Lead author, Corresponding author   Language:Japanese   Publishing type:Research paper (scientific journal)  

    DOI: 10.18919/jkg.73.11_507

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  • Assessments of prolonged effects of desflurane and sevoflurane on motor learning deficits in aged AppNL-G-F/NL-G-F mice Reviewed International journal

    Niikura R, Miyazaki T, Takase K, Sasaguri H, Saito T, Saido TC, Goto T

    Molecular brain   15 ( 1 )   32 - 32   2022.4

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    Authorship:Corresponding author   Language:English   Publishing type:Research paper (scientific journal)   Publisher:Springer Science and Business Media LLC  

    Abstract

    As the proportion of elderly in society increases, so do the number of older patients undergoing surgical procedures. This is concerning as exposure to anesthesia has been identified as a risk factor for Alzheimer’s disease (AD). However, the causal relationship between clinical AD development and anesthesia remains conjectural. Preclinical studies have demonstrated that anesthesia, such as halothane, isoflurane, and sevoflurane, induces AD-like pathophysiological changes and cognitive impairments in transgenic mouse models of AD. Desflurane does not have these effects and is expected to have more potential for use in elderly patients, yet little is known about its effects, especially on non-cognitive functions, such as motor and emotional functions. Thus, we examined the postanesthetic effects of desflurane and sevoflurane on motor and emotional function in aged AppNL−G−F/NL−G−F (App-KI) mice. This is a recently developed transgenic mouse model of AD exhibiting amyloid β peptide (Aβ) amyloidosis and a neuroinflammatory response in an age-dependent manner without non-physiological amyloid precursor protein (APP) overexpression. Mice were subjected to a short behavioral test battery consisting of an elevated plus maze, a balance beam test, and a tail suspension test seven days after exposure to 8.0% desflurane for 6 h or 2.8% sevoflurane for 2 h. App-KI mice showed significant increments in the percentage of entry and time spent in open arms in the elevated plus maze, increments in the number of slips and latency to traverse for the balance beam test, increments in the limb clasping score, increments in immobile duration, and decrements in latency to first immobile episode for the tail suspension test compared to age-matched wild type (WT) controls. Desflurane- and sevoflurane-exposed App-KI mice showed a delayed decrement in the number of slips for each trial in the balance beam test, while air-treated App-KI mice rapidly improved their performance, and increased their clasping behavior in the tail suspension test. Furthermore, App-KI inhibited the change in membrane GluA3 following exposure to anesthetics in the cerebellum. These results suggest high validity of App-KI mice as an animal model of AD.

    DOI: 10.1186/s13041-022-00910-1

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    Other Link: https://link.springer.com/article/10.1186/s13041-022-00910-1/fulltext.html

  • ポストコロナ時代の若者を理解する新しい発達理論の必要性-行動科学が果たす役割 Invited Reviewed

    髙瀨堅吉

    行動科学   60 ( 1 )   1 - 11   2022.3

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  • シチズンサイエンスの社会実装 - B&C スタイルへの拡大- Invited Reviewed

    髙瀨 堅吉, 渡部 麻衣子, 林 和弘

    STI Horizon   7 ( 3 )   22 - 27   2021.8

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  • Exploratory analyses of postanesthetic effects of desflurane using behavioral test battery of mice. Reviewed International journal

    Niikura R, Miyazaki T, Yonezaki K, Uchimoto K, Takase K, Goto T

    Behavioural pharmacology   31 ( 7 )   597 - 609   2020.5

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    Halogenated ethers, such as desflurane, sevoflurane, and isoflurane, are known to exert an array of effects besides sedation. However, the postanesthetic effects of desflurane remain undiscovered as no study has explored these effects systematically. Phenotypic screening using behavioral test batteries is a powerful method to identify such effects. In the present study, we behaviorally phenotyped desflurane-treated mice to investigate postanesthetic effects. We applied comprehensive behavioral test batteries measuring sensorimotor functions, anxiety, depression, sociability, attention, and learning abilities, starting 7 days after anesthesia performed with 8.0% desflurane for 6 h. Although our previous study revealed postanesthetic effects of isoflurane in adult mice, in the current study, desflurane-treated mice exhibited no such effects in any behavioral test. To further examine whether desflurane affect behavior in more early time point, we built up a new additional test battery, which carried out 1 day or 3 days after exposure to desflurane. Mice treated with desflurane 1 day before testing showed more slips than other two groups in the first trial, suggesting mild acute side effects of desflurane on motor coordination. These results suggest the safety of desflurane in clinical settings and imply that postanesthetic effects are unique to each halogenated ether.

    DOI: 10.1097/FBP.0000000000000567

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  • Altered behavior in mice overexpressing soluble ST2. Reviewed International journal

    Kikuchi M, Takase K, Hayakawa M, Hayakawa H, Tominaga SI, Ohmori T

    Molecular brain   13 ( 1 )   74   2020.5

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    Psychoneuroimmunological studies have clearly demonstrated that both cellular and humoral immunity are related to major depression. Soluble ST2 is regarded as a key molecule regulating immune system as well as cell proliferation. Indeed, soluble ST2 is reported to reduce IL-33-induced IL-6 and TNF-α production in macrophages and IL-33-induced IL-5 and IL-13 production in type 2 innate lymphoid cells. Elevated serum concentrations of soluble ST2 have been reported in patients with neuropsychiatric disorders, suggesting pathophysiological roles of soluble ST2 in behavioral phenotypes. Nevertheless, the relation between soluble ST2 and depressive behavior remain to be uncovered. To complement this point, we performed broad behavioral phenotyping, utilizing transgenic mice with a high concentration of serum ST2 in the present study. Soluble ST2 overexpression mice (ST2 Tg mice) were generated on a C3H/HeJ background. ST2 Tg mice crossed onto the BALB/c genetic background were used. Before starting tests, each mouse was observed in a clean cage for a general health check and neurological screening tests. In Experiment I, comprehensive behavioral phenotyping was performed to reveal the role of soluble ST2 on sensorimotor functions, anxiety-like behaviors, depression-like behaviors, social behaviors, and learning and memory functions. In Experiment II, to confirm the role of soluble ST2 on depression-like behaviors, a depression test battery (two bottle choice test, forced swimming test, and tail suspension test) was applied. The general health check indicated good general health and normal gross appearance for ST2 Tg mice. Further, the neurological reflexes of all the mice were normal. We found that soluble ST2 overexpression resulted in decreased social interaction. Moreover, depression-like behaviors of ST2 Tg mice were observed in two well-established behavioral paradigms, the forced swimming test and the tail suspension test. Nevertheless, hedonic reaction to sucrose was observed in ST2 Tg mice similar to WT mice. These results suggest the depression in the ST2 Tg mice. In conclusion, through a series of experiments, we established the animal model for assessing role of soluble ST2 in neuropsychiatric disorders, and revealed the possible involvement of soluble ST2 in depressive behavior.

    DOI: 10.1186/s13041-020-00606-4

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  • Differential Roles of Each Orexin Receptor Signaling in Obesity. Reviewed International journal

    Kakizaki M, Tsuneoka Y, Takase K, Kim SJ, Choi J, Ikkyu A, Abe M, Sakimura K, Yanagisawa M, Funato H

    iScience   20   1 - 13   2019.9

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    Orexins are hypothalamic neuropeptides that regulate feeding, energy expenditure, and sleep. Although orexin-deficient mice are susceptible to obesity, little is known about the roles of the orexin receptors in long-term energy metabolism. Here, we performed the metabolic characterization of orexin receptor-deficient mice. Ox1r-deficient mice were resistant to diet-induced obesity, and their food intake was similar between chow and high-fat food. Ox2r-deficient mice exhibited less energy expenditure than wild-type mice when fed a high-fat diet. Neither Ox1r-deficient nor Ox2r-deficient mice showed body weight gain similar to orexin-deficient mice. Although the presence of a running wheel suppressed diet-induced obesity in wild-type mice, the effect was weaker in orexin neuron-ablated mice. Finally, we did not detect abnormalities in brown adipose tissues of orexin-deficient mice. Thus, each orexin receptor signaling has a unique role in energy metabolism, and orexin neurons are involved in the interactive effect of diet and exercise on body weight gain.

    DOI: 10.1016/j.isci.2019.09.003

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  • ヒトのモデル動物としてのマウス・ラットを対象とした行動アセスメント研究の現状と課題 Invited Reviewed

    髙瀨堅吉

    行動科学   56 ( 1 )   21 - 30   2017.9

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  • Neurotransmitters and neuropeptides in gonadal steroid receptor-expressing cells in medial preoptic area subregions of the male mouse. Reviewed

    Tsuneoka Y, Yoshida S, Takase K, Oda S, Kuroda M, Funato H

    Scientific reports   7 ( 1 )   9809   2017.8

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    Language:English   Publishing type:Research paper (scientific journal)   Publisher:NATURE PUBLISHING GROUP  

    Testosterone is involved in male sexual, parental and aggressive behaviors through the androgen receptor (AR) and estrogen receptor (ER) alpha expressed in the brain. Although several studies have demonstrated that ER alpha and AR in the medial preoptic area (MPOA) are required for exhibiting sexual and aggressive behaviors of male mice, the molecular characteristics of ER alpha-and ARexpressing cells in the mouse MPOA are largely unknown. Here, we performed in situ hybridization for neurotransmitters and neuropeptides, combined with immunohistochemistry for ER alpha and AR to quantitate and characterize gonadal steroid receptor-expressing cells in the MPOA subregions of male mice. Prodynorphin, preproenkephalin (Penk), cocaine-and amphetamine-related transcript, neurotensin, galanin, tachykinin (Tac) 1, Tac2 and thyrotropin releasing hormone (Trh) have distinct expression patterns in the MPOA subregions. Gad67-expressing cells were the most dominant neuronal subtype among the ER alpha-and AR-expressing cells throughout the MPOA. The percentage of ER alpha- and AR-immunoreactivities varied depending on the neuronal subtype. A substantial proportion of the neurotensin-, galanin-, Tac2-and Penk-expressing cells in the MPOA were positive for ER alpha and AR, whereas the vast majority of the Trh-expressing cells were negative. These results suggest that testosterone exerts differential effects depending on both the neuronal subtypes and MPOA subregions.

    DOI: 10.1038/s41598-017-10213-4

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  • Moxd1 Is a Marker for Sexual Dimorphism in the Medial Preoptic Area, Bed Nucleus of the Stria Terminalis and Medial Amygdala. Reviewed

    Tsuneoka Y, Tsukahara S, Yoshida S, Takase K, Oda S, Kuroda M, Funato H

    Frontiers in neuroanatomy   11   26   2017.3

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    The brain shows various sex differences in its structures. Various mammalian species exhibit sex differences in the sexually dimorphic nucleus of the preoptic area (SDNPOA) and parts of the extended amygdala such as the principal nucleus of the bed nucleus of the stria terminalis (BNSTpr) and posterodorsal part of the medial amygdala (MePD). The SDN-POA and BNSTpr are male-biased sexually dimorphic nuclei, and characterized by the expression of calbindin D-28K (calbindin 1). However, calbindinimmunoreactive cells are not restricted to the SDN-POA, but widely distributed outside of the SDN-POA. To find genes that are more specific to sexually dimorphic nuclei, we selected candidate genes by searching the Allen brain atlas and examined the detailed expressions of the candidate genes using in situ hybridization. We found that the strong expression of monooxygenase DBH-like 1 (Moxd1) was restricted to the SDN-POA, BNSTpr and MePD. The numbers of Moxd1-positive cells in the SDN-POA, BNSTpr and MePD in male mice were larger than those in female mice. Most of the Moxd1positive cells in the SDN-POA and BNSTpr expressed calbindin. Neonatal castration of male mice reduced the number of Moxd1-positive cells in the SDN-POA, whereas gonadectomy in adulthood did not change the expression of the Moxd1 gene in the SDN-POA in both sexes. These results suggest that the Moxd1 gene is a suitable marker for sexual dimorphic nuclei in the POA, BNST and amygdala, which enables us to manipulate sexually dimorphic neurons to examine their roles in sex-biased physiology and behaviors.

    DOI: 10.3389/fnana.2017.00026

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  • Neonatal isolation augments social dominance by altering actin dynamics in the medial prefrontal cortex. Reviewed

    Tada H, Miyazaki T, Takemoto K, Takase K, Jitsuki S, Nakajima W, Koide M, Yamamoto N, Komiya K, Suyama K, Sano A, Taguchi A, Takahashi T

    Proceedings of the National Academy of Sciences of the United States of America   113 ( 45 )   E7097 - E7105   2016.10

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    Social separation early in life can lead to the development of impaired interpersonal relationships and profound social disorders. However, the underlying cellular and molecular mechanisms involved are largely unknown. Here, we found that isolation of neonatal rats induced glucocorticoid-dependent social dominance over nonisolated control rats in juveniles from the same litter. Furthermore, neonatal isolation inactivated the actin-depolymerizing factor (ADF)/cofilin in the juvenile medial prefrontal cortex (mPFC). Isolation-induced inactivation of ADF/cofilin increased stable actin fractions at dendritic spines in the juvenile mPFC, decreasing glutamate synaptic AMPA receptors. Expression of constitutively active ADF/cofilin in the mPFC rescued the effect of isolation on social dominance. Thus, neonatal isolation affects spines in the mPFC by reducing actin dynamics, leading to altered social behavior later in life.

    DOI: 10.1073/pnas.1606351113

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  • Comprehensive behavioral study and proteomic analyses of CRMP2-deficient mice. Reviewed

    Nakamura H, Yamashita N, Kimura A, Kimura Y, Hirano H, Makihara H, Kawamoto Y, Jitsuki-Takahashi A, Yonezaki K, Takase K, Miyazaki T, Nakamura F, Tanaka F, Goshima Y

    Genes to cells : devoted to molecular & cellular mechanisms   21 ( 10 )   1059 - 1079   2016.9

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    Collapsin response mediator protein 2 (CRMP2) plays a key role in axon guidance, dendritic morphogenesis and cell polarization. CRMP2 is implicated in various neurological and psychiatric disorders. However, invivo functions of CRMP2 remain unknown. We generated CRMP2 gene-deficient (crmp2(-/-)) mice and examined their behavioral phenotypes. During 24-h home cage monitoring, the activity level during the dark phase of crmp2(-/-) mice was significantly higher than that of wild-type (WT) mice. Moreover, the time during the open arm of an elevated plus maze was longer for crmp2(-/-) mice than for WT mice. The duration of social interaction was shorter for crmp2(-/-) mice than for WT mice. Crmp2(-/-) mice also showed mild impaired contextual learning. We then examined the methamphetamine-induced behavioral change of crmp2(-/-) mice. Crmp2(-/-) mice showed increased methamphetamine-induced ambulatory activity and serotonin release. Crmp2(-/-) mice also showed altered expression of proteins involved in GABAergic synapse, glutamatergic synapse and neurotrophin signaling pathways. In addition, SNAP25, RAB18, FABP5, ARF5 and LDHA, which are related genes to schizophrenia and methamphetamine sensitization, are also decreased in crmp2(-/-) mice. Our study implies that dysregulation of CRMP2 may be involved in pathophysiology of neuropsychiatric disorders.

    DOI: 10.1111/gtc.12403

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  • High-fat diet feeding alters olfactory-, social-, and reward-related behaviors of mice independent of obesity. Reviewed

    Takase K, Tsuneoka Y, Oda S, Kuroda M, Funato H

    Obesity (Silver Spring, Md.)   24 ( 4 )   886 - 894   2016.2

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    ObjectiveHigh-fat diet (HFD) consumption causes obesity, which is associated with well-known increased health risks. Moreover, obesity has been associated with altered sensorimotor and emotional behaviors of humans and mice. This study attempted to dissociate the influence of HFD-induced obesity on behaviors from the influence of HFD consumption itself.
    MethodsC57BL male mice were randomly allocated to a low-fat diet (LFD) group, an HFD-induced obesity (DIO) group, or a pair-fed HFD-feeding nonobese (HFD) group. A comprehensive behavioral test battery was performed on all three groups to assess sensorimotor functions, anxiety- and depression-like behaviors, reward-related behaviors, social behaviors, and learning/memory functions.
    ResultsBoth the DIO and HFD groups exhibited disturbed olfaction, blunted ethanol preference, and enhanced social interactions. The DIO group exhibited blunted sucrose preference, shorter latency before falling off during the rotarod test, and a lower response to mechanical stimuli.
    ConclusionsThe HFD-fed nonobese mice showed altered behaviors related to olfaction, social interactions, and rewards that were similar to those of the DIO mice. This finding suggests that HFD consumption alters a variety of behaviors independent of obesity.

    DOI: 10.1002/oby.21441

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  • Postanesthetic Effects of Isoflurane on Behavioral Phenotypes of Adult Male C57BL/6J Mice. Reviewed

    Yonezaki K, Uchimoto K, Miyazaki T, Asakura A, Kobayashi A, Takase K, Goto T

    PloS one   10 ( 3 )   e0122118   2015.3

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    Authorship:Corresponding author   Language:English   Publishing type:Research paper (scientific journal)   Publisher:3  

    Isoflurane was previously the major clinical anesthetic agent but is now mainly used for veterinary anesthesia. Studies have reported widespread sites of action of isoflurane, suggesting a wide array of side effects besides sedation. In the present study, we phenotyped isoflurane-treated mice to investigate the postanesthetic behavioral effects of isoflurane. We applied comprehensive behavioral test batteries comprising sensory test battery, motor test battery, anxiety test battery, depression test battery, sociability test battery, attention test battery, and learning test battery, which were started 7 days after anesthesia with 1.8% isoflurane. In addition to the control group, we included a yoked control group that was exposed to the same stress of handling as the isoflurane-treated animals before being anesthetized. Our comprehensive behavioral test batteries revealed impaired latent inhibition in the isoflurane-treated group, but the concentration of residual isoflurane in the brain was presumably negligible. The yoked control group and isoflurane-treated group exhibited higher anxiety in the elevated plus-maze test and impaired learning function in the cued fear conditioning test. No influences were observed in sensory functions, motor functions, antidepressant behaviors, and social behaviors. A number of papers have reported an effect of isoflurane on animal behaviors, but no systematic investigation has been performed. To the best of our knowledge, this study is the first to systematically investigate the general health, neurological reflexes, sensory functions, motor functions, and higher behavioral functions of mice exposed to isoflurane as adults. Our results suggest that the postanesthetic effect of isoflurane causes attention deficit in mice. Therefore, isoflurane must be used with great care in the clinical setting and veterinary anesthesia.

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  • Grappling with the Core-curriculum Proposal of Behavioral Medicineby JABS, and the Role that JABS should Achieve Invited Reviewed

    TAKASE Kenkichi

    Jpn J Behav Med   20 ( 2 )   52 - 57   2014.10

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    Language:Japanese   Publishing type:Research paper (scientific journal)   Publisher:The Japanese Society of Behavioral Medicine  

    The Educational Commission for Foreign Medical Graduates (ECFMG) has announced that, effective in 2023, physicians applying for ECFMG Certification will be required to graduate from a medical school that has been appropriately accredited. To satisfy this requirement, the physician's medical school must be accredited through a formal process that uses criteria comparable to those established for U.S. medical schools by the Liaison Committee on Medical Education or that uses other globally accepted criteria, such as those put forth by the World Federation for Medical Education. In response to this announcement by ECFMG, we must grapple with the core-curriculum proposal of behavioral medicine which satisfy the items as follows: 1) the core-curriculum achieves the globally accepted criteria, 2) it also follows the international trends of behavioral science and medicine, and 3) it also includes the behavioral science and medicine established originally in Japan. To make the appropriate core-curriculum of behavioral medicine, we must define what behavioral science is. In this article, I proposed the framework of behavioral science and the role that Japanese Association of Behavioral Science (JABS) should achieve through the introduction of the history of JABS, the special fields of the JABS members, and the academic activities of JABS.

    DOI: 10.11331/jjbm.20.52

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    Other Link: https://jlc.jst.go.jp/DN/JALC/10041555216?from=CiNii

  • Meta-analysis of melanin-concentrating hormone signaling-deficient mice on behavioral and metabolic phenotypes. Reviewed

    Takase K, Kikuchi K, Tsuneoka Y, Oda S, Kuroda M, Funato H

    PloS one   9 ( 6 )   e99961   2014.6

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    The demand for meta-analyses in basic biomedical research has been increasing because the phenotyping of genetically modified mice does not always produce consistent results. Melanin-concentrating hormone (MCH) has been reported to be involved in a variety of behaviors that include feeding, body-weight regulation, anxiety, sleep, and reward behavior. However, the reported behavioral and metabolic characteristics of MCH signaling-deficient mice, such as MCH-deficient mice and MCH receptor 1 (MCHR1)-deficient mice, are not consistent with each other. In the present study, we performed a meta-analysis of the published data related to MCH-deficient and MCHR1-deficient mice to obtain robust conclusions about the role of MCH signaling. Overall, the meta-analysis revealed that the deletion of MCH signaling enhanced wakefulness, locomotor activity, aggression, and male sexual behavior and that MCH signaling deficiency suppressed non-REM sleep, anxiety, responses to novelty, startle responses, and conditioned place preferences. In contrast to the acute orexigenic effect of MCH, MCH signaling deficiency significantly increased food intake. Overall, the meta-analysis also revealed that the deletion of MCH signaling suppressed the body weight, fat mass, and plasma leptin, while MCH signaling deficiency increased the body temperature, oxygen consumption, heart rate, and mean arterial pressure. The lean phenotype of the MCH signaling-deficient mice was also confirmed in separate meta-analyses that were specific to sex and background strain (i.e., C57BL/6 and 129Sv). MCH signaling deficiency caused a weak anxiolytic effect as assessed with the elevated plus maze and the open field test but also caused a weak anxiogenic effect as assessed with the emergence test. MCH signaling-deficient mice also exhibited increased plasma corticosterone under non-stressed conditions, which suggests enhanced activity of the hypothalamic-pituitary-adrenal axis. To the best of our knowledge, the present work is the first study to systematically compare the effects of MCH signaling on behavioral and metabolic phenotypes.

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  • A subset of thalamocortical projections to the retrosplenial cortex possesses two vesicular glutamate transporter isoforms, VGluT1 and VGluT2, in axon terminals and somata Reviewed

    Oda S, Funato H, Sato F, Adachi-Akahane S, Ito M, Takase K, Kuroda M

    The Journal of comparative neurology   522 ( 9 )   2089 - 2106   2014.4

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    Vesicular glutamate transporter isoforms, VGluT1-VGluT3, accumulate glutamate into synaptic vesicles and are considered to be important molecules in glutamatergic transmission. Among them, VGluT2 mRNA is expressed predominantly throughout the dorsal thalamus, whereas VGluT1 mRNA is expressed in a few thalamic nuclei. In the thalamic nuclei that project to the retrosplenial cortex (RSC), VGluT1 mRNA is expressed strongly in the anterodorsal thalamic nucleus (AD), is expressed moderately in the anteroventral and laterodorsal thalamic nuclei, and is not expressed in the anteromedial thalamic nucleus. Thus, it has been strongly suggested that a subset of thalamocortical projections to RSC possesses both VGluT1 and VGluT2. In this study, double-labeled neuronal somata showing both VGluT1 and VGluT2 immunolabelings were found exclusively in the ventral region of AD (vAD). Many double-labeled axon terminals were also found in two major targets of vAD, the rostral part of the reticular thalamic nucleus and layers Ia and III-IV of the retrosplenial granular b cortex (RSGb). Some were also found in layer Ia of the retrosplenial granular a cortex (RSGa). These axon terminals contain significant amounts of both VGluTs. Because the subset of thalamocortical projections to RSC has a unique molecular basis in the glutamatergic transmission system, it might play an important role in the higher cognitive functions processed in the RSC. Furthermore, double-labeled axon terminals of a different type were distributed in RSGb and RSGa. Because they are small and the immunoreactivity of VGluT2 is significantly weaker than that of VGluT1, they seemed to be a subset of corticocortical terminals. J. Comp. Neurol. 522:2089-2106, 2014. (c) 2013 Wiley Periodicals, Inc.

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  • Developmental trajectory of contextual learning and 24-h acetylcholine release in the hippocampus. Reviewed

    Takase K, Sakimoto Y, Kimura F, Mitsushima D

    Scientific reports   4   3738   2014.1

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    To determine the developmental trajectory of hippocampal function in rats, we examined 24-h changes in extracellular acetylcholine (ACh) levels and contextual learning performance. Extracellular ACh significantly correlated with spontaneous behavior, exhibiting a 24-h rhythm in juvenile (4-week-old), pubertal (6-week-old), and adult (9- to 12-week-old) rats. Although juveniles of both sexes exhibited low ACh levels, adult males had higher ACh levels than adult females. Moreover, juveniles exhibited much more spontaneous activity than adults when they showed equivalent ACh levels. Similarly, juveniles of both sexes exhibited relatively low contextual learning performance. Because contextual learning performance was significantly increased only in males, adult males exhibited better performance than adult females. We also observed a developmental relationship between contextual learning and ACh levels. Scopolamine pretreatment blocked contextual learning and interrupted the correlation. Since long-term scopolamine treatment after weaning impaired contextual learning in juveniles, the cholinergic input may participate in the development of hippocampus.

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  • Monoaminergic and neuropeptidergic neurons have distinct expression profiles of histone deacetylases. Reviewed

    Takase K, Oda S, Kuroda M, Funato H

    PloS one   8 ( 3 )   e58473   2013.3

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    Monoaminergic and neuropeptidergic neurons regulate a wide variety of behaviors, such as feeding, sleep/ wakefulness behavior, stress response, addiction, and social behavior. These neurons form neural circuits to integrate different modalities of behavioral and environmental factors, such as stress, maternal care, and feeding conditions. One possible mechanism for integrating environmental factors through the monoaminergic and neuropeptidergic neurons is through the epigenetic regulation of gene expression via altered acetylation of histones. Histone deacetylases (HDACs) play an important role in altering behavior in response to environmental factors. Despite increasing attention and the versatile roles of HDACs in a variety of brain functions and disorders, no reports have detailed the localization of the HDACs in the monoaminergic and neuropeptidergic neurons. Here, we examined the expression profile of the HDAC protein family from HDAC1 to HDAC11 in corticotropin-releasing hormone, oxytocin, vasopressin, agouti-related peptide (AgRP), pro-opiomelanocortin (POMC), orexin, histamine, dopamine, serotonin, and noradrenaline neurons. Immunoreactivities for HDAC1,- 2,- 3,- 5,- 6,- 7,- 9, and - 11 were very similar among the monoaminergic and neuropeptidergic neurons, while the HDAC4, - 8, and - 10 immunoreactivities were clearly different among neuronal groups. HDAC10 expression was found in AgRP neurons, POMC neurons, dopamine neurons and noradrenaline neurons but not in other neuronal groups. HDAC8 immunoreactivity was detected in the cytoplasm of almost all histamine neurons with a pericellular pattern but not in other neuropeptidergic and monoaminergic neurons. Thus, the differential expression of HDACs in monoaminergic and neuropeptidergic neurons may be crucial for the maintenance of biological characteristics and may be altered in response to environmental factors.

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  • 遺伝子改変マウス行動表現型解析の現状とその課題―MCH/ MHCR1ノックアウトマウス行動表現型解析を例として― Invited Reviewed

    高瀬堅吉, 小田哲子, 黒田優, 船戸弘正

    行動科学   51 ( 2 )   143 - 154   2013.3

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  • Effects of volatile anesthetics on the circadian rhythms of rat hippocampal acetylcholine release and locomotor activity. Reviewed

    Kikuchi T, Tan H, Mihara T, Uchimoto K, Mitsushima D, Takase K, Morita S, Goto T, Andoh T, Kamiya Y

    Neuroscience   237   151 - 160   2013.2

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    General anesthesia is occasionally associated with postoperative complications such as sleep disorder, drowsiness, or mood alterations. Hippocampal acetylcholine (ACh), the extracellular level of which increases during the dark (active) phase and decreases during the light (rest) phase in rats, is thought to be associated with locomotor activity and be crucial for learning and memory. Propofol, an intravenous anesthetic, is known to shift the circadian rhythms of physiological parameters including locomotor activity and body temperature in both rodents and humans, while the effects of volatile anesthetics on the circadian rhythm largely remain unclear. The present study examined the effects of isoflurane anesthesia on the diurnal changes in hippocampal ACh release and locomotor activity in rats. Rats were divided into three groups: a light-phase anesthesia group (LA group), a dark-phase anesthesia group (DA group), and a control group. They were exposed to a 12-h light/12-h dark environment and anesthetized with 1.4% isoflurane for 4. h during the middle of the light phase (LA group) and dark phase (DA group). Simultaneous measurement of hippocampal ACh by microdialysis and locomotor activity were done for 60. h under free-moving conditions. Hippocampal ACh release and locomotor activity showed a clear circadian rhythm. In the DA group, but not in the LA group, the diurnal variation in ACh release was significantly disturbed and a more than 2-h phase-advance in locomotor activity was observed. There was a significant correlation between hippocampal ACh release and locomotor activity, and isoflurane anesthesia disrupted it even after anesthesia was discontinued. This study revealed that the levels and circadian rhythms of hippocampal ACh release and locomotor activity were more sensitive to isoflurane anesthesia when it was administered during the active phase. Our findings suggest that anesthesia exerts differential effects on the regulation of circadian rhythms depending on the circadian phase. © 2013 IBRO.

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  • Arachidonate cascade in the intensive insulin therapy for critically Ill patients with sepsis: Roles of prostaglandins on hyperglycemia-impaired immunity Reviewed

    Yagami T, Yamamoto Y, Kohma H, Takase K

    Letters in drug design & discovery   9 ( 6 )   557 - 567   2012.7

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    Intensive insulin therapy to control blood glucose level increases survival among critically ill patients in intensive care unit and hospital. Hyperglycemia is potentially harmful because it acts as a procoagulant, induces insulin resistance, causes apoptosis, impairs neutrophil function, increases the infection rate and is associated with the risk of morbidity and mortality. Hyperglycemia and insulin resistance are virtually universally in sepsis, which is the leading cause of death in critically ill patients. Initially, sepsis is characterized by a hyper-inflammatory response; but as sepsis persists, there is a shift toward an anti-inflammatory immunosuppressive state. The intensive insulin therapy also reduces the infection rate and the mortality in septic patients. Arachidonate cascade is one of the factors associated with hyperglycemia, sepsis and infection. The cascade is involved in the upregulation of proinflammtory cytokines and the dysfunction of immune cells. Especially, we focused on prostaglandin D-2 (PGD(2)), which is produced from innate and adaptive immune cells. PGD(2) is non-enzymatically metabolized to 15-deoxy-Delta(12,14)-PGJ(2), (15d-PGJ(2)). 15d-PGJ(2) is an endogenous ligand for the nuclear receptor, peroxysome proliferators-activated receptor gamma (PPAR gamma) and induces apoptosis in the both immune cells. This review presents plausible roles of arachidonate cascade in hyperglycemia-impaired immunity. Furthermore, we shed light on therapeutic potentials of PPAR gamma ligands for critically ill patients under the insulin resistant state.

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  • Maternal deprivation in the middle of a stress hyporesponsive period decreases hippocampal calcineurin expression and causes abnormal social and cognitive behaviours in adult male Wistar rats: Relevance to negative symptoms of schizophrenia. Reviewed

    Takase K, Yamamoto Y, Yagami T

    Behavioural brain research   232 ( 1 )   306 - 315   2012.6

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    Adverse experiences in early life profoundly influence the developing nervous, endocrine, and immune systems, and also affect human behaviour during adult life and are considered in the pathogenesis of psychiatric disorders. Numerous studies have provided evidence that maternal deprivation in the middle of a stress hyporesponsive period (SHRP) causes multiple behavioural and physiological abnormalities that mimic positive symptoms of schizophrenia in humans. To investigate the neurochemical characteristics of maternal deprivation in the middle of the SHRP in the context of a possible animal model of the symptoms of schizophrenia, we examined calcineurin expression in the hippocampus of maternally deprived rats. To investigate other behavioural characteristics, we behaviourally phenotyped the rats by applying a comprehensive behavioural test battery. The results indicate that maternal deprivation in the middle of the SHRP has no effects on general health, neurological reflexes, sensory function, or motor function, but does have sex-specific effects on a type of anxiety-related behaviour in the open field test and male-specific effects on hippocampal calcineurin expression, social behaviour, and objective memory function. An interpretation of our results and previous studies in the context of the neurodevelopmental hypothesis of schizophrenia suggests that maternal deprivation in the middle of the SHRP in rats models some positive and negative aspects of schizophrenia. The findings regarding the sex-specific effects of maternal deprivation in the middle of the SHRP may become a strong tool for investigating sex differences in the pathogenesis and pathology of schizophrenia in humans. (C) 2012 Elsevier B.V. All rights reserved.

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  • Disrupted cortical function underlies behavior dysfunction due to social isolation. Reviewed

    Miyazaki T, Takase K, Nakajima W, Tada H, Ohya D, Sano A, Goto T, Hirase H, Malinow R, Takahashi T

    The Journal of clinical investigation   122 ( 7 )   2690 - 2701   2012.6

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    Stressful events during early childhood can have a profound lifelong influence on emotional and cognitive behaviors. However, the mechanisms by which stress affects neonatal brain circuit formation are poorly understood. Here, we show that neonatal social isolation disrupts molecular, cellular, and circuit developmental processes, leading to behavioral dysfunction. Neonatal isolation prevented long-term potentiation and experience-dependent synaptic trafficking of alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptors normally occurring during circuit formation in the rodent barrel cortex. This inhibition of AMPA receptor trafficking was mediated by an increase of the stress glucocorticoid hormone and was associated with reduced calcium/calmodulin-dependent protein kinase type II (CaMKII) signaling, resulting in attenuated whisker sensitivity at the cortex. These effects led to defects in whisker-dependent behavior in juvenile animals. These results indicate that neonatal social isolation alters neuronal plasticity mechanisms and perturbs the initial establishment of a normal cortical circuit, which potentially explains the long-lasting behavioral effects of neonatal stress.

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  • Cytotoxicity of troglitazone through PPARγ-independent pathway and p38 MAPK pathway in renal cell carcinoma. Reviewed

    Fujita M, Yagami T, Fujio M, Tohji C, Takase K, Yamamoto Y, Sawada K, Yamamori M, Okamura N

    Cancer letters   312 ( 2 )   219 - 227   2011.12

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    Agonists of peroxisome proliferator-activated receptor gamma (PPAR gamma) have been examined as chemopreventive and chemotherapeutic agents. The aim was to investigate the cytotoxicity of troglitazone (TGZ) and its mechanisms in terms of PPAR gamma dependency and the p38 mitogen-activated protein kinase (MAPK) pathway in three human renal cell carcinoma (RCC) cell lines, 786-O, Caki-2 and ACHN cells. TGZ induced apoptosis and exerted cytotoxicity in a PPAR gamma-independent manner. We demonstrated that TGZ activated the p38 MAPK pathway and was involved in the cytotoxicity of TGZ. It was also revealed that TGZ induced G(2)/M cell cycle arrest through activation of p38 MAPK. (C) 2011 Elsevier Ireland Ltd. All rights reserved.

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  • 空間学習能力の性差出現に関わる海馬を神経支配するコリン作動性ニューロンの機能的性差 Reviewed

    高瀬堅吉

    心理学評論   53 ( 4 )   526 - 544   2011.3

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  • Proteomic identification of protein targets for 15-deoxy-Δ(12,14)-prostaglandin J2 in neuronal plasma membrane. Reviewed

    Yamamoto Y, Takase K, Kishino J, Fujita M, Okamura N, Sakaeda T, Fujimoto M, Yagami T

    PloS one   6 ( 3 )   e17552   2011.3

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    15-deoxy-Delta(12,14)-prostaglandin J(2) (15d-PGJ(2)) is one of factors contributed to the neurotoxicity of amyloid beta (A beta), a causative protein of Alzheimer's disease. Type 2 receptor for prostaglandin D-2 (DP2) and peroxysome-proliferator activated receptor gamma (PPAR gamma) are identified as the membrane receptor and the nuclear receptor for 15d-PGJ(2), respectively. Previously, we reported that the cytotoxicity of 15d-PGJ(2) was independent of DP2 and PPAR gamma, and suggested that 15d-PGJ(2) induced apoptosis through the novel specific binding sites of 15d-PGJ(2) different from DP2 and PPAR gamma. To relate the cytotoxicity of 15d-PGJ(2) to amyloidoses, we performed binding assay [H-3]15d-PGJ(2) and specified targets for 15d-PGJ(2) associated with cytotoxicity. In the various cell lines, there was a close correlation between the susceptibilities to 15d-PGJ(2) and fibrillar A beta. Specific binding sites of [H-3]15d-PGJ(2) were detected in rat cortical neurons and human bronchial smooth muscle cells. When the binding assay was performed in subcellular fractions of neurons, the specific binding sites of [H-3]15d-PGJ(2) were detected in plasma membrane, nuclear and cytosol, but not in microsome. A proteomic approach was used to identify protein targets for 15d-PGJ(2) in the plasma membrane. By using biotinylated 15d-PGJ(2), eleven proteins were identified as biotin-positive spots and classified into three different functional proteins: glycolytic enzymes (Enolase2, pyruvate kinase M1 (PKM1) and glyceraldehyde 3-phosphate dehydrogenase (GAPDH)), molecular chaperones (heat shock protein 8 and T-complex protein 1 subunit alpha), cytoskeletal proteins (Actin beta, F-actin-capping protein, Tubulin beta and Internexin alpha). GAPDH, PKM1 and Tubulin beta are A beta-interacting proteins. Thus, the present study suggested that 15d-PGJ(2) plays an important role in amyloidoses not only in the central nervous system but also in the peripheral tissues.

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  • Fibroblast growth factor 2 induces apoptosis in the early primary culture of rat cortical neurons. Reviewed

    Yagami T, Takase K, Yamamoto Y, Ueda K, Takasu N, Okamura N, Sakaeda T, Fujimoto M

    Experimental cell research   316 ( 14 )   2278 - 2290   2010.8

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    In the central nervous system, fibroblast growth factor 2 (FGF2) is known to have important functions in cell survival and differentiation. In addition to its roles as a neurotrophic factor, we found that FGF2 caused cell death in the early primary culture of cortical neurons. FGF2-induced neuronal cell death showed apoptotic characters, e.g., chromatin condensation and DNA fragmentation. The ultrastructural morphology of FGF2-treated neurons indicated apoptotic features such as progressive cell shrinkage, blebbing of the plasma membrane, loss of cytosolic organelles, clumping of chromatin, and fragmentation of DNA. Tyrosine kinase inhibitors significantly rescued neurons from FGF2-induced apoptosis. FGF2 potentiated a marked influx of Ca(2+) into neurons before apoptosis. Both a calcium chelator and L-type voltage-sensitive Ca(2+) channel (L-VSCC) blockers attenuated FGF2-induced apoptosis, whereas other blockers of VSCCs such as N-type and P/Q-types did not. Blockers of L-VSCCs significantly suppressed FGF2-enhanced Ca(2+) influx into neurons. Moreover, FGF2 also generated reactive oxygen species (ROS) before apoptosis. Radical scavengers reduced not only the FGF2-generated ROS, but also the FGF2-induced Ca(2+) influx and apoptosis. In conclusion, we demonstrated that FGF2 caused apoptosis via L-VSCCs in the early neuronal culture. (C) 2010 Elsevier Inc. All rights reserved.

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  • Nature-nurture problem on the sex difference in the spatial ability Invited Reviewed

    Behavioral science research   48 ( 1 )   69 - 82   2009.12

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  • Activational and organisational effects of gonadal steroids on sex-specific acetylcholine release in the dorsal hippocampus. Reviewed

    Mitsushima D, Takase K, Takahashi T, Kimura F

    Journal of neuroendocrinology   21 ( 4 )   400 - 405   2009.3

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    Acetylcholine (ACh) release in the dorsal hippocampus increases during stress, exploration or learning, exhibiting sex-specific 24-h release profile. We review the role of gonadal steroids on the ACh release in the dorsal hippocampus. In our studies, we found that male rats showed higher extracellular ACh levels than females, but gonadectomy decreased ACh levels in both sexes of rats and subsequently eliminated the sex difference. To examine the sex difference under comparable gonadal steroid levels, we implanted steroid capsules after gonadectomy. Oestradiol supplementation maintained circulating oestradiol to the levels in proestrous female rats, whereas testosterone capsules maintained circulating testosterone to the levels similar to intact male rats. Under comparable gonadal steroids levels, ACh levels were sex-specific. Testosterone replacement in orchidectomised rats clearly restored ACh levels, which were greater than ovariectomised testosterone-primed rats. Similarly, oestradiol replacement in ovariectomised rats successfully restored ACh levels, which were higher than orchidectomised oestradiol-primed rats. These results suggest sex-specific activational effects of gonadal steroids on ACh release. To further examine the organisational effect, female pups were neonatally treated with oil, testosterone, oestradiol, or dihydrotestosterone. These rats were bilaterally ovariectomised and a testosterone capsule was implanted at postnatal week 8. Neonatal treatment of either testosterone or oestradiol clearly increased ACh levels, whereas neonatal dihydrotestosterone treatment failed to change levels. These results suggest that: (i) gonadal steroids maintain the sex-specific ACh release in the dorsal hippocampus and (ii) neonatal activation of oestrogen receptors is sufficient to mediate masculinisation of the septo-hippocampal cholinergic system.

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  • Sex-specific 24-h acetylcholine release profile in the medial prefrontal cortex: simultaneous measurement of spontaneous locomotor activity in behaving rats. Reviewed

    Takase K, Kimura F, Yagami T, Mitsushima D

    Neuroscience   159 ( 1 )   7 - 15   2009.3

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    The difference in visual object recognition by males and females suggests a sex-specific function in the medial prefrontal cortex (mPFC). In the present study, we performed an in vivo microdialysis study in three groups of rats (males, diestrous females, and proestrous females) to examine the potential sex difference in acetylcholine (ACh) release in the mPFC. The dialysate was automatically collected from the mPFC every 20 min for 24 In under freely moving conditions and the spontaneous locomotor activity was simultaneously monitored. Although ACh release in the mPFC during the dark phase was significantly greater than during the light phase in both sexes, the female rats consistently exhibited a significantly greater mean ACh release than the males. Spontaneous locomotor activity during the dark phase was also significantly greater than during the light phase in both sexes, but the females exhibited significantly greater spontaneous locomotor activity than the males. In addition, both sexes of rats were found to have significant positive correlations between ACh release and spontaneous locomotor activity, but females were found to have significantly greater correlation coefficients than males. Stereological methods were used to examine the number of choline acetyltransferase immunoreactive cells in the nucleus basalis magnocellularis and the horizontal diagonal band of Broca. The number of choline acetyltransferase immunoreactive cells in the nucleus basalis magnocellularis was also greater in females than males, suggesting a contribution to the higher ACh release in females. In contrast, no sex difference in the choline acetyltransferase immunoreactive cells was observed in the horizontal diagonal band of Broca. This is the first report to show a sex difference in the 24-h ACh release profile in the mPFC of behaving rats. (C) 2009 IBRO. Published by Elsevier Ltd. All rights reserved.

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  • Gonadal steroids maintain 24 h acetylcholine release in the hippocampus: organizational and activational effects in behaving rats. Reviewed

    Mitsushima D, Takase K, Funabashi T, Kimura F

    The Journal of neuroscience : the official journal of the Society for Neuroscience   29 ( 1 )   3808 - 3815   2009.3

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    Extracellular acetylcholine (ACh) levels in the dorsal hippocampus increases during learning or exploration, exhibiting a sex-specific 24 h release profile. To examine the activational effect of gonadal steroid hormones on the sex-specific ACh levels and its correlation with spontaneous locomotor activity, we observed these parameters simultaneously for 24 h. Gonadectomy severely attenuated the ACh levels, whereas the testosterone replacement in gonadectomized males or 17 beta-estradiol replacement in gonadectomized females successfully restored the levels. 17 beta-Estradiol-priming in gonadectomized males could not restore the ACh levels, and testosterone replacement in gonadectomized females failed to raise ACh levels to those seen in testosterone-primed gonadectomized males, revealing a sex-specific activational effect. Spontaneous locomotor activity was not changed in males by gonadectomy or the replacement of gonadal steroids, but 17 beta-estradiol enhanced the activity in gonadectomized females. Gonadectomy severely reduced the correlation between ACh release and activity levels, but the testosterone replacement in gonadectomized males or 17 beta-estradiol replacement in gonadectomized females successfully restored it. To further analyze the sex-specific effect of gonadal steroids, we examined the organizational effect of gonadal steroids on the ACh release in female rats. Neonatal testosterone or 17 beta-estradiol treatment not only increased the ACh levels but also altered them to resemble male-specific ACh release properties without affecting levels of spontaneous locomotor activity. We conclude that the activational effects of gonadal steroids maintaining the ACh levels and the high correlation with spontaneous locomotor activity are sex-specific, and that the organizational effects of gonadal steroids suggest estrogen receptor-mediated masculinization of the septo-hippocampal cholinergic system.

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  • Gonadal steroid hormones maintain the stress-induced acetylcholine release in the hippocampus: simultaneous measurements of the extracellular acetylcholine and serum corticosterone levels in the same subjects. Reviewed

    Mitsushima D, Takase K, Funabashi T, Kimura F

    Endocrinology   149 ( 2 )   802 - 811   2008.2

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    To examine the role of gonadal steroid hormones in the stress responses of acetylcholine (ACh) levels in the hippocampus and serum corticosterone levels, we observed these parameters simultaneously in intact, gonadectomized, or gonadectomized steroid-primed rats. In both sexes of rats, neither gonadectomy nor the replacement of gonadal steroid hormone affected the baseline levels of ACh. However, gonadectomy severely attenuated the stress response of ACh, whereas the replacement of corresponding gonadal hormone successfully restored the response to intact levels. The gonadal hormones affected the serum corticosterone levels in a different manner; the testosterone replacement in orchidectomized rats suppressed the baseline and the stress response of corticosterone levels, whereas the 17 beta-estradiol replacement in ovariectomized rats increased the levels. We further found that letrozole or flutamide administration in intact male rats attenuated the stress response of ACh. In addition, flutamide treatment increased the baseline levels of corticosterone, whereas letrozole treatment attenuated the stress response of corticosterone. Moreover, we found a low positive correlation between the ACh levels and corticosterone levels, depending on the presence of gonadal steroid hormone. We conclude that: 1) gonadal steroid hormones maintain the stress response of ACh levels in the hippocampus, 2) the gonadal steroid hormone independently regulates the stress response of ACh in the hippocampus and serum corticosterone, and 3) the sex-specific action of gonadal hormone on the cholinergic stress response may suggest a neonatal sexual differentiation of the septohippocampal cholinergic system in rats.

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  • Postpubertal feeding experience affects sex-specific spatial ability in rats. Reviewed

    Takase K, Mitsushima D, Funabashi T, Kimura F

    Physiology & behavior   93 ( 3 )   553 - 559   2008.2

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    We previously reported that feeding with powdered diet after weaning (3 weeks of age) enhanced spatial ability, and increased the amount of acetylcholine (ACh) released in the dorsal hippocampus in female rats. In the present study, to specify the time when feeding conditions caused these effects, a radial 8-arm maze task and an in vivo microdialysis study were performed in both sexes of rats. In rats fed standard laboratory diet (i.e., pelleted diet), males learned the radial 8-arm maze faster than females. Moreover, the ACh release showed a distinct diurnal rhythm which was high during the dark phase and low during the light phase, but males showed a greater amount of ACh released in the dorsal hippocampus than females. However, in rats fed powdered diet after 6 weeks of age, no significant sex differences were observed in the radial 8-arm maze task or in the amount of ACh released, since feeding with powdered diet enhanced spatial ability, and increased the amount of ACh released only in females. These results suggest that feeding conditions after 6 weeks of age may contribute to the sex difference in the spatial ability associated with the changes in the amount of ACh released in the dorsal hippocampus in rats. (C) 2007 Elsevier Inc. All rights reserved.

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  • Sex difference in the 24-h acetylcholine release profile in the premotor/supplementary motor area of behaving rats. Reviewed

    Takase K, Mitsushima D, Funabashi T, Kimura F

    Brain research   1154   105 - 115   2007.6

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    The sex differences in various motor functions suggest a sex-specific neural basis in the nonprimary or primary motor area. To examine the sex difference in the 24-h profile of acetylcholine (ACh) release in the rostral frontal cortex area 2 (rFr2), which is equivalent to the premotor/supplementary motor area in primates, we performed an in vivo microdialysis study in both sexes of rats fed pelleted or powdered diet. The dialysate was automatically collected from the rFr2 for 24 h under freely moving conditions. Moreover, the number of cholinergic neurons in the nucleus basalis magnocellularis (NBM) was examined. Further, to confirm the relation between ACh release in the rFr2 and motor function, the spontaneous locomotor activity was monitored for 24 h. Both sexes showed a distinct 24-h rhythm of ACh release, which was high during the dark phase and low during the light phase. Female rats, however, showed a greater ACh release and more cholinergic neurons in the NBM than male rats. Similarly, spontaneous locomotor activity also showed a 24-h rhythm, which paralleled the changes in ACh release in both sexes, and these changes were again greater in female rats than in male rats. In addition, feeding with powdered diet significantly increased the ACh release and spontaneous locomotor activity. The present study is the first to report the sex difference in the 24-h profile of ACh release in the rFr2 in rats. The sex specific ACh release in the rFr2 may partly contribute to the sex difference in motor function in rats. (C) 2007 Elsevier B.V. All rights reserved.

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  • Sex differences in the basolateral amygdala: the extracellular levels of serotonin and dopamine, and their responses to restraint stress in rats. Reviewed

    Mitsushima D, Yamada K, Takase K, Funabashi T, Kimura F

    The European journal of neuroscience   24 ( 11 )   3245 - 3254   2006.12

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    The sex difference in the emotional response to stress suggests a sex-specific stress response in the amygdala. To examine the sex difference in extracellular levels of serotonin (5HT) and dopamine (DA) in the basolateral amygdala (BLA) and their responses to restraint stress, in vivo microdialysis studies were performed in male and female rats. In experiment I, dialysates were collected from the BLA at 15-min intervals under the freely moving condition. Mean extracellular levels of 5HT or DA in the BLA were higher in male rats than in female rats. In experiment II, rats were subjected to restraint stress for 60 min to examine the stress response of 5HT or DA levels. Although restraint stress significantly increased extracellular 5HT levels in both sexes of rats, female rats showed a greater response than male rats. Moreover, restraint stress significantly increased extracellular DA levels in female rats, but not in male rats. In experiment III, rats were subjected to restraint stress for 30 min to examine behavioral responses to restraint stress. Although no sex difference was observed in the number of audible vocalizations, male rats defecated a larger number of fecal pellets than female rats. In experiment IV, rats were tested for freezing behavior to examine contextual fear responses. Conditioned male rats showed a longer freezing time than conditioned female rats. We found sex differences in the extracellular levels of 5HT and DA in the BLA and their responses to restraint stress, which may be involved in the sex-specific emotional response to stress in rats.

    DOI: 10.1111/j.1460-9568.2006.05214.x

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  • Feeding with powdered diet after weaning increases visuospatial ability in association with increases in the expression of N-methyl-D-aspartate receptors in the hippocampus of female rats. Reviewed

    Takase K, Funabashi T, Mogi K, Mitsushima D, Kimura F

    Neuroscience research   53 ( 2 )   169 - 175   2005.10

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    We determined whether feeding with powdered diet improved the visuospatial ability in female rats by checking the expression of N-methyl-D-aspartate receptor (NMDAR) subunit 1 (NR1) mRNA in the hippocampus. In rats fed standard pelleted diet, males performed better than females in a radial 8-arm maze task as we reported previously. We found that the expression of NR1 mRNA, which may be the key mediator in visuospatial ability in the hippocampus, was also higher in males than in females. However, in rats fed powdered diet, no sex difference was seen in the radial 8-arm maze task and the expression of NR1 mRNA in the hippocampus, since feeding with powdered diet improved the visuospatial ability with increases in the expression of NR1 mRNA in the hippocampus in females. We suggest that the sex difference in visuospatial ability is at least in part due to feeding conditions. (c) 2005 Elsevier Ireland Ltd and the Japan Neuroscience Society. All rights reserved.

    DOI: 10.1016/j.neures.2005.06.013

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  • Feeding with powdered diet after weaning affects sex difference in acetylcholine release in the hippocampus in rats. Reviewed

    Takase K, Mitsushima D, Masuda J, Mogi K, Funabashi T, Endo Y, Kimura F

    Neuroscience   136 ( 2 )   593 - 599   2005.10

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    We have reported in the past that female rats fed a powdered diet showed better spatial learning and memory functions than female rats a fed pelleted diet. In the present study, we examined the effects of feeding with powdered diet on acetylcholine release in the hippocampus in both sexes of rats. After weaning (3 weeks of age), rats were fed either standard pelleted diet or powdered diet, and after maturation (9-12 weeks of age), they were used in an in vivo microdialysis study, in which no eserine (a cholinesterase inhibitor) was added to the perfusate. The dialysate was collected from the dorsal hippocampus at 20-min intervals underfreely moving conditions for more than 24 h. Acetylcholine in the dialysate was measured by high performance liquid chromatography. As we reported previously, the acetylcholine release showed a clear daily rhythm in both sexes, and males showed significantly greater acetylcholine release in the hippocampus than females in rats fed pelleted diet. Conversely, in rats fed powdered diet, no sex difference in the acetylcholine release was observed, since feeding with powdered diet significantly increased the acetylcholine release only in females. To further examine the number of cholinergic neurons in the medial septum and horizontal limb of the diagonal band of Broca, immunocytochemistry for choline acetyltransferase was performed in both sexes of rats fed either standard pelleted diet or powdered diet. However, neither sex nor feeding conditions affect the number of choline acetyltransferase immunoreactive cells in the areas. These results suggest that powdered diet after weaning enhances spontaneous acetylcholine release in the hippocampus in female rats without changes in the number of cholinergic neurons in the areas. It is possible that this effect of feeding contributes to improve the performance in spatial learning and memory functions in female rats fed powdered diet. (c) 2005 Published by Elsevier Ltd on behalf of IBRO.

    DOI: 10.1016/j.neuroscience.2005.08.012

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Books

  • 心理学検定 公式問題集[2024年度]

    日本心理学諸学会連合, 心理学検定局( Role: Joint author6 神経・生理)

    実務教育出版  2023.10  ( ISBN:4788961083

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    Total pages:479   Language:Japanese  

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  • 動物心理学入門: 動物行動研究から探るヒトのこころの世界

    日本動物心理学会(監修)( Role: Contributor2-2 経験で脳は変わるの?ー知能の発達とエピジェネティクス)

    有斐閣  2023.7  ( ISBN:4641174881

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    Total pages:156  

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  • 心理学検定 専門用語&人名辞典

    日本心理学諸学会連合 心理学検定局( Role: Contributor)

    実務教育出版  2023.6  ( ISBN:4788961075

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    Total pages:423  

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  • 心理学検定 公式問題集[2023年度版]

    日本心理学諸学会連合, 心理学検定局( Role: Joint author6 神経・生理)

    実務教育出版  2022.12  ( ISBN:4788961067

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    Total pages:481   Language:Japanese  

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  • 神経・生理心理学:脳から心を理解する(公認心理師の基本を学ぶテキスト)

    川畑直人, 大島剛, 郷式徹, 中島恵子, 矢島潤平( Role: Contributor第2章 神経系ー心の生物学的基盤)

    ミネルヴァ書房  2022.12  ( ISBN:4623087115

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    Total pages:224  

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  • 公認心理師 国家試験対策全科

    内山伊知郎, 松田英子( Role: Contributorchapter 21 人体の構造と機能および疾病)

    金芳堂  2022.12  ( ISBN:476531927X

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    Total pages:556  

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  • 応用心理学ハンドブック

    応用心理学ハンドブック編集委員会, 藤田主一, 古屋健, 角山剛, 谷口泰富, 深澤伸幸, 日本応用心理学会( Role: Contributor3章 Topic5 動物行動における感情評価)

    福村出版  2022.9  ( ISBN:4571200870

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    Total pages:858   Language:Japanese  

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  • 神経・生理心理学 (放送大学教材)

    髙瀨堅吉( Role: Sole author)

    放送大学教育振興会  2022.3  ( ISBN:4595323174

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    Total pages:300   Language:Japanese  

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  • 心理学検定 公式問題集[2022年度]

    日本心理学諸学会連合 心理学検定局( Role: Joint author6 神経・生理)

    実務教育出版  2022.3  ( ISBN:4788961059

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    Total pages:484   Language:Japanese  

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  • 有斐閣現代心理学辞典

    子安増生, 丹野義彦, 箱田裕司( Role: Contributor)

    有斐閣  2021.2  ( ISBN:4641002665

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    Total pages:996  

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  • ソーシャルディスタンスでデジタル化する社会の闇 本当の自分がわからない若者、捨てられる50代

    髙瀨堅吉( Role: Sole author)

    徳間書店  2020.12  ( ISBN:4198651051

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    Total pages:232   Language:Japanese  

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  • 心理職のための身につけておきたい生物学の基礎知識

    髙瀨堅吉( Role: Sole author)

    誠信書房  2020.10  ( ISBN:441441671X

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    Total pages:182   Language:Japanese  

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  • 神経・生理心理学ー基礎と臨床,わたしとあなたをつなぐ「心の脳科学」ー

    坂本敏郎, 上北朋子, 田中芳幸( Role: Contributor第9章 心の病と発達系の障害)

    ナカニシヤ出版  2020.5  ( ISBN:477951472X

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    Total pages:176   Language:Japanese  

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  • AIと共生する人間とテクノロジーのゆくえ(Miraikanトークス)

    大隅典子, 紺野登, 行方史郎, 高瀬堅吉, 山田胡瓜, 千葉雅也, タカハシショウコ, 中尾悠里, 駒井章治, 行木陽子, 須田桃子, サリー楓( Role: Joint author心理学者から見たデジタル社会とヒトの心)

    集英社  2020.4 

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    人の知性はどう変わる? AI(人工知能)に関し、人がどういうふうに関わり、どう使っていくのか。12人の慧眼が照らし出すAI社会の甘夢あるいは悪夢。何か答えを求めるのではなく、議論して探る、それ自体が目的となる会議のありようを模索するアゴラ市民会議。その一環として2019年に実施したイベント「どんな未来を生きていく? ~AIと共生する人間とテクノロジーのゆくえ~」を電子書籍化したものです。

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    Other Link: https://www.amazon.co.jp/%EF%BC%A1%EF%BC%A9%E3%81%A8%E5%85%B1%E7%94%9F%E3%81%99%E3%82%8B%E4%BA%BA%E9%96%93%E3%81%A8%E3%83%86%E3%82%AF%E3%83%8E%E3%83%AD%E3%82%B8%E3%83%BC%E3%81%AE%E3%82%86%E3%81%8F%E3%81%88%EF%BC%88%EF%BC%AD%EF%BD%89%EF%BD%92%EF%BD%81%EF%BD%89%EF%BD%8B%EF%BD%81%EF%BD%8E%E3%83%88%E3%83%BC%E3%82%AF%E3%82%B9%EF%BC%89-%E9%9B%86%E8%8B%B1%E7%A4%BEe%E9%81%B8%E6%9B%B8%E3%83%88%E3%83%BC%E3%82%AF%E3%82%B9-%E5%A4%A7%E9%9A%85%E5%85%B8%E5%AD%90-ebook/dp/B086WDM4XH

  • 心理学検定 公式問題集[2020年度版]

    日本心理学諸学会連合 心理学検定局( Role: Joint author6 神経・生理)

    実務教育出版  2020.3  ( ISBN:4788961008

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    Total pages:480  

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  • 健康心理学事典

    日本健康心理学会( Role: Contributor第2章 生理学的メカニズム(発達・加齢))

    丸善出版  2019.10  ( ISBN:4621303767

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    Total pages:746   Language:Japanese  

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  • 国試・改訂コアカリ対応 地域医療学入門

    日本医学教育学会地域医療教育委員会・全国地域医療教育協議会 合同編集委員会( Role: Joint author第3章-3 医療に関連した人文・社会科学領域)

    診断と治療社  2019.7  ( ISBN:4787823841

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    Total pages:184   Language:Japanese  

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  • 〈自閉症学〉のすすめ:オーティズム・スタディーズの時代

    野尻英一, 高瀬堅吉, 松本卓也( Role: Joint editor)

    ミネルヴァ書房  2019.4  ( ISBN:4623086488

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    Total pages:392   Language:Japanese  

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  • 心理学検定 公式問題集[2019年度版]

    日本心理学諸学会連合 心理学検定局( Role: Joint author6 神経・生理)

    実務教育出版  2019.3  ( ISBN:4788961040

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    Total pages:480   Language:Japanese  

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  • 看護を学ぶ人のための心理学

    遠藤公久( Role: Contributor第3章 学習)

    弘文堂  2019.2  ( ISBN:4335651856

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    Total pages:296   Language:Japanese  

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  • 第2巻 心理学概論 (公認心理師の基礎と実践)

    繁桝算男( Role: Contributor2章 心の生物学的基盤)

    遠見書房  2018.4  ( ISBN:4866160527

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    Total pages:200  

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  • 心理学検定 公式問題集[2018年度版]

    日本心理学諸学会連合 心理学検定局( Role: Joint author6 神経・生理)

    実務教育出版  2018.3  ( ISBN:4788961032

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    Total pages:480  

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  • 生理心理学と精神生理学 第I巻 基礎

    堀忠雄, 尾﨑久記, 坂田省吾, 山田冨美雄( Role: Contributor5章 脳と行動の遺伝子操作)

    北大路書房  2017.6  ( ISBN:4762829722

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    Total pages:320  

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  • 心理学検定 公式問題集[2017年度版]

    日本心理学諸学会連合 心理学検定局( Role: Joint author6 神経・生理)

    実務教育出版  2017.3  ( ISBN:4788960982

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  • 医と知の航海

    永井良三, 自治医科大学総合教育部門( Role: Contributor心理 心を理解する、心を調べる~心理学でわかること、わからないこと~)

    西村書店  2016.6  ( ISBN:4890134646

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    Total pages:354  

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  • 心理学検定 一問一答問題集[B領域編]

    日本心理学諸学会連合 心理学検定局( Role: Contributor6 神経・生理)

    実務教育出版  2016.6  ( ISBN:4788961024

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    Total pages:240  

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  • 心理学検定 公式問題集[2016年度版]

    日本心理学諸学会連合 心理学検定局( Role: Joint author6 神経・生理)

    実務教育出版  2016.3  ( ISBN:4788960974

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    Total pages:480  

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  • ラットの行動解析ハンドブック

    高瀬堅吉, 柳井修一, 山口哲生( Role: Supervisor (editorial))

    西村書店  2015.9  ( ISBN:4890134565

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    Total pages:435  

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  • 心理学検定 基本キーワード 改訂版

    日本心理学諸学会連合 心理学検定局( Role: Joint author6 神経・生理)

    実務教育出版  2015.5  ( ISBN:4788960966

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    Total pages:376  

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  • 心理学検定 公式問題集[2015年度版]

    日本心理学諸学会連合 心理学検定局( Role: Joint author6 神経・生理)

    実務教育出版  2015.3  ( ISBN:4788960958

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    Total pages:413  

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  • 心理学検定 公式問題集[2014年度版]

    日本心理学諸学会連合 心理学検定局( Role: Joint author6 神経・生理)

    実務教育出版  2014.3  ( ISBN:4788960907

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    Total pages:436  

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  • 心理学検定 公式問題集[2013年度版]

    日本心理学諸学会連合 心理学検定局( Role: Joint author6 神経・生理)

    実務教育出版  2013.3  ( ISBN:4788960893

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    Total pages:440  

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  • トランスジェニック・ノックアウトマウスの行動解析

    高瀬堅吉, 柳井修一( Role: Supervisor (editorial))

    西村書店  2012.9  ( ISBN:4890134271

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    Total pages:407  

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  • 心理学検定 公式問題集[2012年度版]

    日本心理学諸学会連合 心理学検定局( Role: Joint author6 神経・生理)

    実務教育出版  2012.3  ( ISBN:4788960885

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    Total pages:436  

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  • カラー版 ボロン ブールペープ 生理学

    泉井亮, 河南洋, 久保川学( Role: Joint translator9部 生殖系)

    西村書店  2011.9  ( ISBN:4890134131

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    Total pages:1363  

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  • エピソードでつかむ老年心理学 (シリーズ生涯発達心理学)

    大川一郎, 宇都宮博, 日下菜穂子, 奥村由美子, 土田宣明( Role: Sole authorTopics11 脳科学と加齢、Topics25 100歳老人の心理的特徴)

    ミネルヴァ書房  2011.4  ( ISBN:4623058956

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    Total pages:291  

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  • 心理学検定 公式問題集[2011年度版]

    日本心理学諸学会連合 心理学検定局( Role: Joint author6 神経・生理)

    実務教育出版  2011.3  ( ISBN:4788960877

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    Total pages:440  

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  • Horizons in Neuroscience Research

    Takase K, Mitsushima D( Role: Joint authorSex difference in learning and memory: effects of sex differentiation, development, and environments on the forebrain cholinergic system)

    Nova Science Pub Inc  2010.9  ( ISBN:1608768767

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    Total pages:293  

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  • 心理学検定 基本キーワード

    日本心理学諸学会連合 心理学検定局( Role: Joint author6 神経・生理)

    実務教育出版  2009.6  ( ISBN:4788960834

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    Total pages:324  

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  • 心理学検定 公式問題集

    日本心理学諸学会連合 心理学検定局( Role: Joint author6 神経・生理)

    実務教育出版  2009.4  ( ISBN:4788960826

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    Total pages:376  

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MISC

  • 2040年の科学・学術と社会を見据えていま取り組むべき10の課題 Reviewed

    日本学術会議若手アカデミー

    見解   2023.9

  • イノベーション人材の育成を促進する中長期的リモデリング戦略

    日本学術会議若手アカデミー

    記録   2023.9

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  • 人文・社会科学の研究による社会的インパクト~事例調査に基づく評価のあり方の検討~ Reviewed

    日本学術会議科学者委員会研究評価分科会

    報告   2023.9

  • <座談会>従来の科学コミュニケーションの枠を超えるシチズンサイエンスの可能性と今後に向けた対話 Invited

    出演者:髙瀨堅吉, 中村征樹 司会:立花浩司

    日本の科学者   58 ( 1 )   5 - 16   2023.1

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    Authorship:Lead author   Language:Japanese   Publishing type:Article, review, commentary, editorial, etc. (scientific journal)  

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  • 性差研究に基づく科学技術・イノベーションの推進 Reviewed

    日本学術会議科学者委員会男女共同参画分科会(性差に基づく科学技術イノベーションの検討小分科会)

    見解   2022.11

  • 新型コロナウイルスの感染拡大で顕在化した「ケアの孤立」と心理学の高等教育 Invited

    髙瀨堅吉

    中央評論   74 ( 1 )   32 - 39   2022.4

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  • 学術の振興に寄与する研究評価を目指して-望ましい研究評価に向けた課題と展望- Reviewed

    日本学術会議科学者委員会研究評価分科会

    提言   2021.11

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    File: kohyo-25-t312-1.pdf

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  • マウスの行動表現型解析をツールとした基礎・臨床医学研究との連携 Invited

    髙瀨堅吉

    東邦医学会雑誌   2021

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  • シチズンサイエンスを推進する社会システムの構築を目指して Reviewed

    日本学術会議若手アカデミー

    提言   2020.9

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    File: kohyo-24-t297-2.pdf

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  • 学術とSDGsのネクストステップ ー社会とともに考えるためにー Reviewed

    日本学術会議科学と社会委員会科学と社会企画分科会

    報告   2020.9

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    File: kohyo-24-h200904.pdf

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  • 社会のための心理学~心理学高等教育の入口と出口~

    日本学術会議心理学・教育学委員会社会のための心理学分科会

    記録   2020.9

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  • 科学的エビデンスを主体としたスポーツの在り方 - Evidence Based Sports for Diverse Humanity (EBS4DH) - Reviewed

    日本学術会議科学的エビデンスに基づく「スポーツの価値」の普及の在り方に関する委員会

    提言   2020.6

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    File: kohyo-24-t290-5.pdf

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  • 科学的エビデンスに基づく「スポーツの価値」の普及の在り方 Reviewed

    日本学術会議科学的エビデンスに基づく「スポーツの価値」の普及の在り方に関する委員会

    回答   2020.6

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  • 心の基礎研究を通して社会を診る Invited

    髙瀨堅吉

    学術の動向   25 ( 4 )   104 - 111   2020.4

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  • 心理学におけるシチズン・サイエンスの可能性 Invited

    髙瀨堅吉

    学術の動向   23 ( 11 )   40 - 45   2018.11

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  • 科学者は時代とどう向き合うのか vol.2 「若手研究者の考える科学者の“今”そして“未来”」 Invited

    狩野光伸, 岸村顕広, 平田佐智子, 髙瀨堅吉

    SciREX Quarterly   7   2017.12

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  • 第2回若手科学者サミット開催報告 Invited

    髙瀨堅吉

    学術の動向   22 ( 9 )   110 - 111   2017.9

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  • 発達段階・性別特異的行動異常の生物・心理・社会モデルに基づく検討-動物とヒトの研究、基礎と臨床をつなぐ古くて新しい心理学研究モデルの提案- Invited

    高瀬堅吉

    立命館文学   641   233 - 243   2015.3

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  • 視床とコリン作動性ネットワーク Invited

    高瀬堅吉, 黒田優

    Clinical neuroscience   30 ( 6 )   655 - 657   2012.5

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  • 飼育環境によって性差が生まれる海馬の空間認知機能:新脳の関わる認知機能には本来,性差はない Invited

    貴邑冨久子, 美津島大, 遠藤豊, 舩橋利也, 高瀬堅吉

    性差と医療   3 ( 12 )   1289 - 1291   2006.11

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Presentations

  • シチズンサイエンス推進の現状及び課題 Invited

    髙瀨堅吉

    日本科学者会議 第22回東京科学シンポジウム  2023.12 

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    Event date: 2023.12    

    Language:Japanese   Presentation type:Oral presentation (invited, special)  

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  • オンラインイベントのコロナ前・中・後の変化と世界中の認定心理士と繋がる未来 Invited

    髙瀨堅吉

    公益社団法人日本心理学会 認定心理士の会オンラインイベント  2023.12 

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    Event date: 2023.12    

    Language:Japanese   Presentation type:Symposium, workshop panel (nominated)  

    File: 231209_online.pdf

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  • HITE研究者フラッシュトーク Invited

    髙瀨堅吉

    HITE2023カンファレンス「HITE RE-UNION!」  2023.12 

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    Event date: 2023.12    

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  • 硬直性自律位相連鎖(RAPS)を基盤とした自閉症スペクトラム障害における諸症状の包括的理解 Invited

    髙瀨堅吉

    京都大学 発達科学セミナー  2023.11 

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  • 最前線の若手研究者と考える2040年の未来 Invited

    髙瀨堅吉

    日本科学振興協会 年次大会2023「会いに行ける科学者フェス」 ステージ企画「最前線の若手研究者と考える2040年の未来」  2023.10 

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    Event date: 2023.10    

    Language:Japanese   Presentation type:Symposium, workshop panel (nominated)  

    File: 最前線の若手研究者と考える2040年の未来.pdf

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  • サイエンスを基盤とした共創事業推進に必要な人材-研究と開発を繋ぐナレッジ&スキルをどう備えるのか- Invited

    髙瀨堅吉

    日本科学振興協会 年次大会2023「会いに行ける科学者フェス」 シンポジウム「サイエンスを基盤とした共創事業推進に必要な人材-研究と開発を繋ぐナレッジ&スキルをどう備えるのか-」  2023.10 

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  • 自閉症スペクトラム障害の理論研究「硬直性自律位相連鎖(RAPS)を基盤とした自閉症スペクトラム障害における諸症状の包括的理解」

    髙瀨堅吉

    日本心理学会第87回大会 シンポジウム「自閉症スペクトラム障害の理論・基礎・臨床~病態の神経・生理心理学的基盤をめぐる最新の研究動向」  2023.9 

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    Event date: 2023.9    

    Language:Japanese   Presentation type:Symposium, workshop panel (public)  

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  • 学術会議若⼿アカデミーと考えるリサーチ・アドミニストレーションの未来

    髙瀬堅吉

    RA協議会 第9回年次大会  2023.8 

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    Event date: 2023.8    

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  • 日本学術会議からの提言についての概要ー学術の振興に寄与する研究評価を目指して- Invited

    髙瀨堅吉

    第31回日本医学会総会 学術プログラム U40委員会企画「将来に向けた医学研究評価のあり方について考える」  2023.4 

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    Event date: 2023.4    

    Language:Japanese   Presentation type:Oral presentation (invited, special)  

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  • 高齢者の孤独について考える Invited

    髙瀨堅吉

    日本心理学会 公開シンポジウム「誰一人取り残さない」社会の実現のために:心理学者が考える「持続可能な開発目標(SDGs)」 第3回「孤独について考える」  2023.3 

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    Language:Japanese   Presentation type:Oral presentation (invited, special)  

    File: sympo2022_sdgs_3.pdf

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  • 基礎研究における統制環境がつくりだす脳機能の性差 Invited

    髙瀨堅吉

    日本発達心理学会第34回大会 大会委員会企画シンポジウム「環境がつくる性-その基礎と臨床」  2023.3 

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    Event date: 2023.3    

    Language:Japanese   Presentation type:Symposium, workshop panel (nominated)  

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  • 父母によるチームをどうやってサポートするのか? 近所のおじいちゃん、おばあちゃんに代わるシチズンサイエンス Invited

    髙瀨堅吉

    日本赤ちゃん学会第22回学術集会 指定演題ラウンドテーブル「赤ちゃんの発達をサポートする父母によるチームの現状と課題」  2022.7 

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    Language:Japanese   Presentation type:Symposium, workshop panel (nominated)  

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  • シチズンサイエンスとは Invited

    髙瀨堅吉

    日本科学振興協会第1回総会・キックオフミーティング パネルディスカッション「日本の科学をもっと元気に:誰もが科学する社会を創ろう!」  2022.6 

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    Language:Japanese   Presentation type:Symposium, workshop panel (nominated)  

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  • オープンサイエンス時代における科学と市民の関わり方-サイロエフェクトを打破する可能性があるシチズンサイエンス Invited

    髙瀨堅吉

    Japan Open Science Summit 2022 市民科学「オープンサイエンスのサイロエフェクトを打破するために:シチズンサイエンスと超学際研究からのアプローチ」  2022.6 

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  • ニューロダイバーシティと社会-心理学の視点から Invited

    髙瀨堅吉

    第1回自閉症学超会議! パネルディスカッション「ニューロダイバーシティと社会」  2022.4 

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  • 網羅的行動テストバッテリーを用いた麻酔薬の新規作用の探索 Invited

    高瀬堅吉, 宮崎智之, 新倉怜, 後藤隆久

    日本臨床麻酔学会第41回大会 シンポジウム「若手研究者による麻酔科領域研究の新機軸」  2021.11 

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    Language:Japanese   Presentation type:Symposium, workshop panel (nominated)  

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  • 産後のメンタルヘルスにおける心理支援と課題 Invited

    髙瀨堅吉

    日本助産学会 2021サマーセミナー「産後のメンタルヘルス支援を変えていこう」  2021.9 

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  • 認定心理士の会のこれまで-心理学ワールド全体の動向とシチズンサイエンスとの関係 Invited

    髙瀨堅吉

    日本心理学会第85回大会 シンポジウム「認定心理士の会のこれまでとこれからオープンサイエンス時代におけるシチズンサイコロジストの役割」  2021.9 

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    Language:Japanese   Presentation type:Symposium, workshop panel (nominated)  

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  • 心理学におけるシチズンサイエンスの展開 Invited

    髙瀨堅吉

    Japan Open Science Summit 2021 総合関連「学術会議若手アカデミーと考えるオープンサイエンス」  2021.6 

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  • 日本心理学会認定心理士が行う3つのタイプのシチズンサイエンスーA&C・B&C・C&Cー Invited

    髙瀨堅吉

    Japan Open Science Summit 2021 テクノロジー関連「研究開発推進における市民の役割」  2021.6 

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    Language:Japanese   Presentation type:Symposium, workshop panel (nominated)  

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  • マウスの行動表現型解析をツールとした基礎・臨床医学研究との連携 Invited

    髙瀨堅吉

    第74回東邦医学会総会(招聘講演)  2020.11 

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  • シチズンサイエンス推進に向けたこれまでの活動報告と実践における課題 Invited

    髙瀨堅吉

    科学技術社会論学会第18回年次研究大会 オーガナイズドセッション「オープンサイエンス・市民科学・サイエンスカフェ・SDGs」  2019.11 

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  • 免疫関連たんぱく質ST2過剰発現マウスの行動表現型解析 Invited

    髙瀨堅吉

    日本心理学会第83回大会 シンポジウム「免疫系の行動科学・心理学」  2019.9 

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  • 認定心理士の会の新たな取り組み‐シチズン・サイエンス Invited

    髙瀨堅吉

    日本心理学会第82回大会 シンポジウム「シチズン・サイエンスを通じた“心理学の再現性の危機”への挑戦‐認定心理士の会の新たな取り組み‐」  2018.9 

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  • 公認心理師・心理学研究者が潜在的フィールドで活躍する際に求められる知識・技術 Invited

    髙瀨堅吉

    日本心理学会第82回大会 シンポジウム「公認心理師・心理学研究者の潜在的フィールド‐広がる活躍の場と求められる知識・技術‐」  2018.9 

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    Language:Japanese   Presentation type:Symposium, workshop panel (nominated)  

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  • 母子の分離が脳機能に与える影響 Invited

    髙瀨堅吉

    北海道心理学会第64回大会 シンポジウム「子供を取り囲む環境‐育まれる心、育む心‐」  2017.10 

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  • 認定心理士の会 今後の活動の展望 Invited

    髙瀨堅吉

    日本心理学会第81回大会 シンポジウム「社会で活きている心理学‐認定心理士の会/認定心理士の活動をアカデミアへ還流する‐」  2017.9 

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  • Research evaluation disparities: possibly influenced by research field and generation? International conference

    Takase K

    Y-KAST - YAJ Bilateral Workshop "Institutional and Scientific Challenges for Young Scientists in Asia"  2017.3 

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  • ヒトのモデル動物としてのマウス・ラットを対象とした行動アセスメント研究の現状と課題

    高瀬堅吉

    日本行動科学学会第33回ウィンターカンファレンス シンポジウム  2017.2 

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  • Meta-analysis of genetically modified mice on behavioral and biological phenotypes Invited International conference

    Takase K, Kikuchi K, Funato H

    31st International Congress of Psychology (ICP2016) Invited symposia “Frontiers in the psychological research using animal models -Harmonized translational study elucidating the operating principles underlying human psychological processes-”  2016.7 

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  • 医学と心理学の学際先端領域におけるキャリア形成の枠組み Invited

    高瀬堅吉

    日本心理学会第79回大会 シンポジウム「広がる心理学‐学際性の先端領域と新しいキャリア形成の枠組み‐」  2015.9 

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  • 社会行動障害への多角的アプローチ‐動物からヒト、基礎から臨床‐(ストレス不応期の母子分離ストレスが社会行動に与える影響) Invited

    高瀬堅吉

    日本心理学会第79回大会 シンポジウム「社会行動障害への多角的アプローチ‐動物からヒト、基礎から臨床‐」  2015.9 

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  • 人間の生涯発達の理解を目指す生理心理学研究‐乳幼児(仔)期~思春期・成体期‐

    高瀬堅吉

    日本心理学会第78回大会 シンポジウム「人間の生涯発達の理解を目指す生理心理学研究」  2014.9 

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  • 行動医学のコアカリキュラム提案に向けたJABSの取り組みと求められる役割 Invited

    高瀬堅吉

    第20回日本行動医学会学術総会 シンポジウム「行動医学のコアカリキュラムの提案」  2014.3 

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    Language:Japanese   Presentation type:Symposium, workshop panel (nominated)  

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  • これからの教育心理学を考える‐動物実験とどのように付き合うのか?‐

    高瀬堅吉

    日本心理学会第77回大会 シンポジウム「これからの教育心理学を考える‐動物実験、生物学的指標とどのように付き合うのか?‐」  2013.9 

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  • 摂食関連ペプチドMCHの多様な役割と、各行動に与える効果量のメタ分析 Invited

    高瀬堅吉

    日本行動科学学会2012年度年次大会 シンポジウム「日本におけるこれからの行動科学‐求められる学際性と国際性‐」  2012.9 

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  • 養育環境・生活環境によってつくられる高次脳機能の性差 Invited

    高瀬堅吉

    日本行動科学学会第25回ウィンターカンファレンス(25周年記念大会) シンポジウム「神経科学と行動科学を繋ぐ架け橋‐尖鋭的若手研究者からのメッセージ‐」  2009.3 

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Awards

  • 若手研究奨励賞

    2005.7   日本神経内分泌学会  

    高瀬堅吉

Research Projects

  • 若者の生きづらさを解消し高いウェルビーイングを実現するメタケアシティ共創拠点

    2022.11 - 2032.3

    文部科学省  共創の場形成支援プログラム(COI-NEXT)(本格型) 

    宮﨑智之

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    Authorship:Coinvestigator(s) 

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  • 多様性寛容の共創システム開発 -『違いがあっても大丈夫』と共育しあえるコミュニティ構築‐

    Grant number:SIPICP23A02  2023.11 - 2028.3

    内閣府  戦略的イノベーション創造プログラム(SIP) 

    清家理

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    Authorship:Coinvestigator(s) 

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  • パーソナリティ特性が運動学習機能に与える影響の神経基盤解明

    2020.4 - 2025.3

    文部科学省  科学研究費補助金(基盤研究(C)) 

    板井美浩

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  • 位相連鎖の可変性が個体行動に与える影響の包括的検討-ヘッブの理論の拡張を目指して

    Grant number:19K03368  2019.4 - 2025.3

    文部科学省  科学研究費補助金(基盤研究(C))  基盤研究(C)  自治医科大学

    高瀬堅吉

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    Grant type:Competitive

    本研究では、成体期の雄性マウスに逆転学習課題を課し、その後、感覚運動機能、不安行動、社会行動、抑うつ行動を調べる複数のテストを組み合わせた行動テストバッテリーを課す。すべての実験終了後に、逆転学習課題の結果から位相連鎖の可変性が高い個体、低い個体を抽出し、行動テストバッテリーにおける各個体の結果を比較することで、個体行動全般における位相連鎖の役割を明らかにすることを目的に実験を行う。1クール(5週間)につき10匹を対象にサンプリングを行う。総計200匹まで、最大で20クールにわたり行動解析を実施してデータを得る。
    昨年度までに逆転学習機能測定で用いるバーンズ迷路テストのセットアップを行い、当該実験系を確立した。また、感覚運動機能測定で用いる視覚性置き直しテスト、プライエル驚愕反射テスト、二瓶選択テスト、嗅覚性馴化脱馴化テスト、フォンフレイ・フィラメントテスト、ホットプレートテスト、ビームテスト、ロータロッドテスト、フットプリントテスト、ワイアハングテストのセットアップも行った。さらに、不安行動測定に用いるオープンフィールドテスト、明暗選択テストや、社会行動測定に用いる社会的行動測定テスト、チューブテスト、性行動測定テスト、最後に、抑うつ行動測定に用いる強制水泳テスト、尾懸垂テストのセットアップも行い、すべての実験系を確立した。
    既に一定数のマウスを行動テストバッテリーにかけ、得られた結果を共分散構造分析によって解析し、逆転学習課題の成績が社会行動を含む、特定の行動特性に関係することを示唆する結果を得ている。研究期間内に上記測定系で総計200匹のマウスの行動解析を終えるよう、現在も実験を進めている。

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  • 潜在保育士の活躍と母親の育児不安解消を目的とした「エビデンスに基づく育児支援環境」の構築

    2022.11 - 2024.3

    中央大学  2022年度第2回 中央大学クラスター形成支援研究助成(産学連携機関間交流支援) 

    高瀬堅吉

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    Authorship:Principal investigator 

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  • ST2過剰発現マウスをモデルとした神経免疫連関の解析

    2020.4 - 2024.3

    文部科学省  科学研究費補助金(基盤研究(C)) 

    菊地元史

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  • 敗血症モデルへの層別化メタボローム解析に基づくPICSメカニズム解明と治療法探索

    2019.4 - 2022.3

    文部科学省  科学研究費補助金(基盤研究(B)) 

    後藤隆久

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    Grant type:Competitive

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  • 人文社会科学の知を活用した、技術と社会の対話プラットフォームとメディアの構築

    2018.10 - 2021.9

    社会技術研究開発センター(RISTEX)  戦略的創造研究推進事業(社会技術研究開発) 

    庄司昌彦

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  • シチズンサイエンスの普及にむけた概念整理とプラットフォーム構築の提案

    2019.8 - 2020.7

    公益財団法人サントリー文化財団  サントリー文化財団研究助成「学問の未来を拓く」 

    中村征樹

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  • 自閉症学(Autism Studies)共創思考サロン

    2018.8 - 2019.3

    大阪大学共創機構 産学共創本部  未来共創思考サロン活動支援プログラム 

    野尻英一

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    Grant type:Competitive

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  • セボフルランによる抗不安効果発現の神経回路同定とその分子メカニズムの解明

    2016 - 2018

    文部科学省  科学研究費補助金(基盤研究(B)) 

    後藤隆久

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  • 性別、発達段階に応じたライフステージ依存性麻酔後効果の検討

    2016 - 2017

    文部科学省  科学研究費補助金(挑戦的萌芽研究) 

    後藤隆久

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  • 肥満誘発性行動変容の分子機構解明

    Grant number:25460317  2013 - 2016

    文部科学省  科学研究費補助金(基盤研究(C))  基盤研究(C)  東邦大学

    高瀬堅吉, 黒田 優, 小田 哲子, 船戸 弘正

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    Grant type:Competitive

    Grant amount: \5070000 ( Direct Cost: \3900000 、 Indirect Cost: \1170000 )

    これまで代表者は、げっ歯類を対象とした網羅的行動解析、生理学的、生化学的解析を展開し、出生後の環境が、個体の学習・記憶機能および統合失調症発症に与える影響について明らかにした。また、現所属機関に赴任後、食環境が脳機能に与える影響とその分子機構について、網羅的行動解析、形態学的解析を組み合わせた手法で検討し、高脂肪食を継続的に給餌したマウスが様々な行動変容を呈することをパイロット研究の結果から示した。多様な行動変容は、脳局所における機能的、形態的変化ではなく、脳全体における変化が仮定され、その原因として脳全体に広く投射する神経修飾物質分泌ニューロンの機能的変化が示唆される。そこで、神経修飾物質を標的とした遺伝子改変マウスの行動表現型に関する複数の報告と、肥満マウスの行動表現型に関するデータを比較したところ、肥満マウスの行動変容はメラニン凝集ホルモン(melanin-concentrating hormone、MCH)を欠損したマウスの行動変容と類似しており、簡易的に測定可能な行動表現型項目において相同性を示すことを示唆した。平成26年度は、パイロット研究で得られた肥満マウスの行動表現型をさらに精緻に検討し、これまでにファスト・スクリーニングで得られるほぼすべての行動表現型についてデータを得ることに成功した。また、MCH欠損マウスとの詳細な比較を行うために、これまで報告されたMCH欠損マウスのほぼすべてのデータに対してメタ分析を行い、肥満マウスが呈する表現型との定量的比較を可能にするメタ分析結果を得た。この結果はPLoS One誌に投稿し、現在Minor Revisionの評価を頂き、再投稿準備中である。これにより、神経修飾物質分泌ニューロンに発現するヒストン脱アセチル化酵素ファミリー発現の検討および肥満マウスの脳のMCH投射領域におけるMCH含有量の測定の準備を整えることができた。

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  • 大脳皮質および海馬の発生学的細胞構築異常と小児の行動異常に関する神経行動学的研究

    Grant number:25380994  2013 - 2015

    文部科学省  科学研究費補助金(基盤研究(C))  基盤研究(C)  姫路獨協大学

    杉岡幸三, 高瀬 堅吉

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    Grant type:Competitive

    Grant amount: \4550000 ( Direct Cost: \3500000 、 Indirect Cost: \1050000 )

    本研究は、学習、注意また活動性などの機能に深く関与する海馬および大脳皮質の機能不全に焦点をしぼり、ラット胎生15、17、19日齢(それぞれM15群、M17群、M19群)に、神経毒性を有するメチルアゾキシメタノール(MAM)を投与することによって、脳の発生学的形態異常を有するADHDもしくはLDモデル動物を作成し、これらの動物に対して、新生児期から成体期に至る様々な時期に、種々の実験パラメーターを用いた多面的行動分析を行うとともに脳の組織学的分析を行った。1)新生児期に分析した正向反射・背地走性では、雌雄のM17群の反射獲得の遅延が観察された、2)離乳期でのOF事態での活動性の分析では、雄のM17群が寡動傾向を示したが、若齢期および成体期では群間に差異はなかった、また3)恐怖条件付け後の、装置に対する文脈記憶を凍結行動を指標として分析したところ、雌のM15およびM17群の凍結行動表出時間は短く、参照記憶の障害を示した。所定の行動実験終了後に測定した脳重は、M15群では対照群の83%、M17群では91%、M19群では95%であった。脳の組織学的分析では、1)M15群では皮質の層構築異常および海馬錐体細胞層の層構築異常および異所性の細胞集塊が観察され、2)M17群では皮質第II層の発達不全が観察された。以上のことは、本研究のM15およびM17群の行動学的結果のいくつかがADHD児で観察される注意欠陥・学習障害と類似するとともに、これらの行動異常が脳の皮質および海馬の発生学的形態異常と関係する可能性を示唆するものである。

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  • オレキシン受容体を介した体重制御と糖代謝制御の遺伝学的神経解剖

    Grant number:25460318  2013 - 2015

    文部科学省  科学研究費補助金(基盤研究(C))  基盤研究(C)  東邦大学

    船戸弘正, 高瀬 堅吉

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    Grant type:Competitive

    Grant amount: \5200000 ( Direct Cost: \4000000 、 Indirect Cost: \1200000 )

    近年、肥満人口が世界的に増加し、我が国でも肥満、糖尿病に関連した社会的損失は甚大である。C57BL/6 マウスは高脂肪高カロリー餌で飼育すると肥満し、耐糖能低下を示すことから、ヒトの肥満および糖尿病のよいモデルとなる。最近、代表者はオレキシンがオレキシン1型受容体と2型受容体を介して、体重調節と糖代謝制御とをそれぞれ独立した経路で制御することを示した。本研究では、オレキシン1 型受容体と2型受容体それぞれの体重調節及び糖代謝への影響を部位特異的遺伝子改変マウスを用いて明らかにする。オレキシン2型受容体アゴニストによる、高脂肪食誘導性肥満抑制作用は野生型マウスおよびオレキシン神経欠損マウスで再現性良く認められている。Fosを用いた検討から、縫線核群内の特定の神経細胞集団が関与していると考えられる。高脂肪食による耐糖能低下を緩和する効果も認められる。このことは、オレキシン2型受容体が創薬標的として大きな可能性を秘めていることを意味する。オレキシンAでは作用はやや弱いが、この点はさらなる検討が必要である。オレキシン1型受容体Floxマウスやオレキシン2型受容体Floxマウスは繁殖コロニーを増やしている。

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  • 網羅的行動テストバッテリーを用いた麻酔薬の新規効能探索

    Grant number:25293330  2013 - 2015

    文部科学省  科学研究費補助金(基盤研究(B))  基盤研究(B)  横浜市立大学

    後藤隆久, 宮崎 智之, 高瀬 堅吉, 内本 一宏

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    Grant type:Competitive

    Grant amount: \18330000 ( Direct Cost: \14100000 、 Indirect Cost: \4230000 )

    まず初めに通常の成体マウスを用いて行動テストバッテリーの構築を行った。動物センターに防音室および行動実験機材の搬入を行い、セットアップを行った。テストバッテリーは大きく分けて、「感覚」、「運動」、「不安」、「鬱様」、「社会性」、「注意」、「記憶」であり、それぞれに2~5種類の行動実験が含まれている。具体的には、「感覚」には、視覚前肢置き直しテスト・二瓶選択テスト・馴化脱馴化テスト・ホットプレートテストが、「運動」には、ローターロッドテスト・ビームテスト・ワイアハングテストが、「不安」には、高架式十字迷路テスト・オープンフィールドテスト・明暗選択テストが、「鬱様」には、ボーソルト強制水泳テスト・尾懸垂テストが、「社会性」には、社会性行動測定テスト・チューブテスト・性行動測定テストが、「注意」には、プレパルスインヒビションテスト・潜在制止テストが、「記憶」には、物体再認テスト・空間認識テスト・社会的再認テスト・恐怖条件付けテストが含めれている。それら2~5種類の行動実験の順番が適切でないと、前の行動実験が翌日以降の行動実験の結果に対して干渉してしまう。従って、私たちが考えた順番で行った各行動実験の結果が、過去に報告された各行動実験の基準値を再現できるかをはじめに確認した。立ち上げより半年でその再現実験が完了したため、続いてイソフルランに曝露したマウスを用いて実験を行った。1.8%のイソフルランに2時間曝露したマウスを用いて上記テストバッテリーを行い、間もなくデータを取り終えるところである。

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  • オレキシンによるエネルギー代謝調節機構の解明

    2012    

    ネスレ栄養科学会議  2012年度研究助成 

    船戸弘正

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  • 摂食・睡眠調節神経回路におけるHDACファミリー発現の検討

    2012    

    東邦大学  東邦大学医学部プロジェクト研究 

    高瀬堅吉

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  • ヒストン脱アセチル化酵素による神経ペプチドを介したマウス行動制御の分子機構解明

    2012    

    東邦大学  医学研究科推進研究費 

    船戸弘正

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  • 適応的な情動性、社会性を育む各性に適した養育環境の検討

    2011 - 2012

    文部科学省  科学研究費補助金(若手研究(B)) 

    高瀬堅吉

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    Grant type:Competitive

    申請者は、ストレス不応期中期に母子分離を施した雄性ラットで不安が高まり、社会性が低下することを発見した。さらに、プロテオーム解析を用いて、この行動異常への関連が示唆される脳内分子を複数列挙することに成功し、その多くが神経細胞の可塑性に関わるタンパク質であることを明らかにした。先行研究は、ストレス不応期中期の母子分離操作が思春期後に統合失調症の陽性症状を模した行動表現型を導くことを報告しており、今回、申請者が得た行動表現型異常は、統合失調症の陰性症状に該当することが明らかとなった。そこで、統合失調症に関わりがあり、かつ、神経細胞の可塑性に関わるタンパク質の発現が統合失調症の責任部位と目される海馬体で変化していると考え、海馬体におけるカルシニューリンの発現量を調べた。その結果、母子分離操作を施された雄性ラットで当該分子の発現量が減少していることが示された。

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  • 多面的行動分析によるADHDモデルラットに関する発生学的および神経行動学的研究

    Grant number:22610024  2010 - 2012

    文部科学省  科学研究費補助金(基盤研究(C))  基盤研究(C)  姫路獨協大学

    杉岡幸三, 高瀬 堅吉, 谷口 泰造

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    Grant type:Competitive

    Grant amount: \4420000 ( Direct Cost: \3400000 、 Indirect Cost: \1020000 )

    本研究は、学習、注意また活動性などの機能に深く関与する海馬、および海馬と密接な線維連絡を有する脳部位の機能不全に焦点をしぼり、ラット胎生15もしくは17日齢(それぞれM15群、M17群)に、神経毒性を有するメチルアゾキシメタノール(MAM)を投与することによって、脳の発生学的形態異常を有するADHDモデル動物を作成し、これらの動物に対して、新生児期から成体期に至る様々な時期に、種々の実験パラメーターを用いた多面的行動分析を行うとともに脳の組織学的分析を行ったものである。成体期に行った本年度の研究においては、1)聴覚性刺激先向提示抑制(PPI)事態での驚愕反射の程度および刺激先向提示による驚愕反射の抑制(PPI)の程度を分析したところ、M15群は雌雄とも有意に大きい驚愕反射を示すとともに、PPIの程度は小さく、注意欠陥の傾向を示した、また2)恐怖条件付け後の、装置に対する文脈記憶を凍結行動を指標として分析したところ、M15群は雌雄とも凍結行動表出時間は短く、参照記憶の障害を示した。脳重に関してM15群では重度の、M17群では軽度の小頭(脳)症を示すとともに、脳の組織学的分析では、1)M15群では皮質の層構築異常および海馬錐体細胞層の層構築異常および異所性の細胞集塊が観察され、2)M17群では皮質第II層の発達不全が観察されるとともに、数例において線条体に変性細胞が観察された。また、カルビンジンによる免疫染色を行ったところ、海馬苔状線維の軸索がM15群およびM17群ともに2層性を示し、この異常な線維連絡はM15群において顕著であった。以上のことから、本研究の行動学的結果のいくつかがADHD児で観察される注意欠陥・学習障害と類似するとともに、これらの行動異常が脳の皮質および海馬の発生学的形態異常と関係する可能性を示唆するものである。

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  • 性ホルモンがオレキシンによる体重制御機構に及ぼす影響の研究

    2011    

    東邦大学  東邦大学医学部プロジェクト研究 

    高瀬堅吉

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  • 15デオキシ-デルタ12,14-プロスタグランジン J2 膜標的分子の同定

    2008 - 2010

    文部科学省  科学研究費補助金(基盤研究(C)) 

    矢上達郎

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    15-deoxy-Δ^<12,14>-prostaglandin J_2(15d-PGJ_2)膜特異的結合部位の神経変性への関与を見出し、プロテオーム解析により11種の標的タンパク質を同定した。標的は、解糖系酵素(神経特異的エノラーゼ・ピルビン酸キナーゼM1・グリセルアルデヒド3リン酸脱水素酵素)、分子シャペロン(熱ショックタンパク質8・Tコンプレックスタンパク質1)および細胞骨格タンパク質(アクチンβ・Fアクチンキャッピングタンパク質、チューブリンβ・インターネキシンα)に分類された。

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  • 社会的隔離が脳内回路形成に及ぼす影響

    2008 - 2010

    文部科学省  科学研究費補助金(基盤研究(B)) 

    高橋琢哉

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    Grant type:Competitive

    幼少時のストレスは生涯にわたって認知情緒行動に影響を及ぼす。しかしながらストレスが幼若時の脳回路形成に及ぼす影響のメカニズムについてはよくわかっていない。本課題では幼若期の社会的隔離が脳回路形成に及ぼす影響を分子レベルで解析している。幼若期の社会的隔離はバレル皮質における経験依存的AMPA受容体シナプス移行を雄においては阻害するが、雌においては阻害しない。

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  • 老化に伴う認知機能の低下を予防する各性に適した生活環境の検討

    2008 - 2009

    文部科学省  科学研究費補助金(若手研究(B)) 

    高瀬堅吉

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    Grant type:Competitive

    本研究は、老化に伴うコリン作動性神経の活動低下を予防するための各性に適した生活環境(食事量、運動量)を同定することを目的として行った。平成21年度に、研究の途上、偶然にも、ラットを乳児期後期から幼児期初期(生後9日目と11日目)の間で低栄養状態にすると、感覚、運動、認知機能は正常であるにも関わらず、雄性ラットのみが、情動性を測定する試験において、不安行動を亢進し、特定箇所を執拗に探索する行動(常同行動)を呈し、さらに、社会性を測定する試験において他個体との関わりを減少させることを発見した(Takase et al., 2009)。これら一連の行動異常は、雌性ラットにはまったく認められなかった。研究結果は、成熟後の脳機能を育むために必要な乳幼児期の生活環境が雌雄で異なることを示している。雄性ラットは、乳幼児期における低栄養状態に非常に脆弱であり、この時期における栄養状態が成熟後の情動性や社会性にまで影響を与えることが示唆された。

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  • 生後の社会的隔離が恐怖条件づけ依存的AMPA受容体シナプス移行へ与える影響の性差

    2007    

    横浜市立大学  研究戦略プロジェクト 

    高瀬堅吉

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  • 性腺ステロイドホルモンが海馬機能に及ぼす影響と性差

    Grant number:18590219  2006 - 2007

    文部科学省  科学研究費補助金(基盤研究(C))  基盤研究(C)  横浜市立大学

    美津島大

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    Grant type:Competitive

    雌雄のウィスター系ラットを実験に用いる。性腺の摘除および性腺ステロイドホルモンの処置は実験の2週間前に行い、20%17β-estradiol封入チューブ(体重250gあたり15mm)、100%testosterone封入チューブ(体重250gあたり30mm)を背側皮下に植え込み、2週間後に実験を行った。In vivo microdialysis実験はペントバルビタール麻酔下で、脳定位固定装置を用いて背側海馬にガイドカニューラを植え込み、固定した。実験前日に、microdialysis用プローブ(Eicom Co.外径0.31mm)をガイドカニューラを介して、背側海馬に刺入した。人工脳脊髄液を1.2μl/分の流速で環流しながら自由行動状態を維持し、翌日からin vivo microdialysis実験を行い、20分ごとに24時間以上連続して脳内環流液の採取とAChの定量を続けた。同時に、各ラットの自発行動量をACTMONITORを用いて数値化し、ACh分泌量との相関解析も行った。その結果、雄性におけるtestosteroneや雌性における17β-estradiolは、ACh分泌量と自発行動量の相関を維持することが判明した。また、この相関は背側海馬のCA1領域で特に顕著であることが判明した。CA3やDG領域でも正の相関は得られたが、CA1領域と比べて有意に低かった。次に、海馬各領...

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  • 性成熟後の養育環境はラットの視空間的能力の性差を形成する

    Grant number:18790170  2006 - 2007

    文部科学省  科学研究費補助金(若手研究(B))  若手研究(B)  横浜市立大学

    高瀬堅吉

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    Grant type:Competitive

    Grant amount: \3600000 ( Direct Cost: \3600000 )

    地図を読む、幾何学の問題を解くなどの視空間的能力において、男性は女性と比べて優位性を示すことが報告されており、このような性差はヒトのみならずサルやラットなどの他の哺乳類でも確認されている。従来、視空間的能力の性差は、脳の性分化により引き起こされると考えられていた。しかし我々は、ラットを用いた一連の研究から、この視空間的能力の性差が生後の環境の影響でつくられることを明らかにした(Endo et al.,1994;Takase et al.,2005a;Takase et al.,2005b)。とは言え、生後のどの時期の環境が視空間的能力の性差をつくるのか未だ不明であった。そこで我々は、雌雄ラットが性成熟する6週齢以降の時期に注目した。この時期はヒトでは思春期以降にあたる(Ojeda and Urbanski,1994)。本研究では視空間的能力という高次脳機能の性差が、思春期以降の環境によってつくられることを明らかにし、思春期以降の環境がどのように視空間的能力の性差をつくるのか、海馬体に注目し、その神経基盤の解明を試みた。現在まで、1)雌雄ラット海馬体内アセチルコリン分泌量は発達に伴い増加すること、2)6週齢以降は雄性ラットの分泌量が雌性ラットに比べて顕著に増加すること、3)その性差は6週齢以降の給餌環境の操作により解消されることを明らかにし、その結果を論文にまとめた(Takas...

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  • 性腺刺激ホルモン放出ホルモンサージ発生器の神経回路の証明

    Grant number:17590209  2005 - 2007

    文部科学省  科学研究費補助金(基盤研究(C))  基盤研究(C)  横浜市立大学

    舩橋利也

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    Grant type:Competitive

    1)鼻板培養によるGnRHサージ発生器モデル 胎生13.5日齢のolfactory placodeを10日回転培養し、サージ発生器を刺激することがin vivoで知られているcAMPを増加させる分解酵素阻害剤を投与した。その結果、容量依存性にGnRHの分泌を増加させた。従って、本モデルは、サージ発生器としての特徴を持っていることが示唆された。
    2)GT1-1細胞によるGnRHサージ発生器モデル GT1-1細胞をカバーグラス上に培養し、カルシウムイメージングと細胞外電気活動の同時測定を、多点電極皿を用いて、同時測定を試みた。その結果、複数のGT1-1細胞の同期した細胞電気活動と、それらと同期したカルシウム変動が観察された。現在、エストロジェンを添加して、GnRH1の分泌変化とカルシウム変動の同時測定を試みている。
    3)グルタミン酸ニューロンとLHサージに関するin vivoの実験 グルタミン酸ニューロンのサージ発生器活動における役割を明らかにする目的で、レンチウイルスを用いて、グルタミン酸型AMPA受容体のシナプスへの移行を阻止するdominant negativeを視索前野に発現させる実験を行った。その結果、LHサージには影響がなかった。しかし、思春期に発現させると成熟後のLHサージが減弱することが明らかとなった。
    4)pCREB とLHサージに関するin vivoの実験 ア...

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  • 海馬体内アセチルコリン分泌動態の生後発達変化と性差発現時期の解明

    2006    

    横浜市立大学  研究戦略プロジェクト 

    高瀬堅吉

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  • 痛みの知覚の性差とそのメカニズム(1)ホルマリン誘発侵害刺激に対するpCREB発現の脳内マッピングとその経時的変化

    Grant number:17590208  2005 - 2006

    文部科学省  科学研究費補助金(基盤研究(C))  基盤研究(C)  横浜市立大学

    貴邑冨久子

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    Grant type:Competitive

    1.ホルマリン侵害刺激に対する痛み行動の性差 正常雄性ラットおよび発情前期ラットの足底皮下にホルマリンを投与すると、二相性の痛み行動が惹起された。その中間相5-10分の痛み行動は、雌性ラットの方が有意に強く、従って、雌性ラットの方がホルマリン侵害刺激に対する感受性の高いこと確認された。またこの性差はエストロジェン依存性であることがわかった。
    2.pCREBによる痛み受容脳領域のマッピングとその経時的変化 雄性ラットおよび発情前期ラットを用いてホルマリンテストを行い、pCREB免疫陽性細胞の発現の変化を、投与前を0分として、5、10,30,120分後に検討した。その結果、分界条床核外側部において、発情前期のラットではpCREB発現が、ホルマリン投与後5分において、有意に増加した。すなわち、行動上の痛覚過敏性と一致して、この領域のCREBがリン酸化されることが明らかとなった。
    3.性腺ステロイドホルモンの役割 ホルマリン投与によるpCREB発現に性差の認められた分界条床核外側部において、雌性ラットの性腺を摘除すると反応性が消失し、エストロジェンを補充すると、ホルマリンに対する反応性が回復した。
    以上、ホルマリン侵害刺激に対する痛み行動には性差が存在し、分界条床核外側部および側座核が関与すること、その性差は、性腺ステロイドホルモンに対する感受性の性差に起因することが推測された。
    さ...

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  • ラット前頭前野の各領域における24時間のアセチルコリン分泌動態と性差

    2005    

    横浜総合医学振興財団  横浜総合医学振興財団萌芽的研究助成 

    高瀬堅吉

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    Grant type:Competitive

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  • 粉エサによる飼育が成熟したラットの脳機能の性差に与える影響

    2004    

    横浜市立大学  横浜市立大学研究奨励交付金 

    高瀬堅吉

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    Grant type:Competitive

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Other

  • Certified Public Psychologist

    2021.3 - Now

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  • Clinical Developmental Psychologist

    2014.4 - Now

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  • JPA Certified Psychologist

    2010.8 - Now

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Teaching Experience

  • Professionalism of Certified Psychologist

    2024.9 - Now   Institution:Chuo University

  • Practical Training in Psychology

    2024.4 - Now   Institution:Chuo University

  • Experimental Medicine

    2024.4 - Now   Institution:Toho University

  • 心理学基礎演習(1)B

    2023.9 - Now   Institution:中央大学

  • Human Body Structure, Function and Diseases

    2023.8 - Now   Institution:Aichi University

  • Graduate Thesis

    2023.4 - Now   Institution:Chuo University

  • 心理学基礎演習(1)A

    2023.4 - Now   Institution:中央大学

  • 心理学特殊研究(2)

    2023.4 - Now   Institution:中央大学

  • 生涯発達心理学特殊研究Ⅱ

    2022.9 - Now   Institution:中央大学大学院

  • 生涯発達心理学特講Ⅱ

    2022.9 - Now   Institution:中央大学大学院

  • 生涯発達心理学演習Ⅱ

    2022.9 - Now   Institution:中央大学大学院

  • 心理学基礎理論Ⅱ

    2022.9 - Now   Institution:中央大学大学院

  • 心理学基礎演習(2)B

    2022.9 - Now   Institution:中央大学

  • 発達心理学

    2022.9 - Now   Institution:中央大学

  • 生涯発達心理学特殊研究Ⅰ

    2022.4 - Now   Institution:中央大学大学院

  • 生涯発達心理学特講Ⅰ

    2022.4 - Now   Institution:中央大学大学院

  • 生涯発達心理学演習Ⅰ

    2022.4 - Now   Institution:中央大学大学院

  • 発達と学習の心理/教育心理学(教職)

    2022.4 - Now   Institution:中央大学

  • 心理学概論/心理学概論(1)

    2022.4 - Now   Institution:中央大学

  • 心理学特殊研究(1)

    2022.4 - Now   Institution:中央大学

  • 心理学基礎演習(2)A

    2022.4 - Now   Institution:中央大学

  • 教育心理学(教育・学校心理学Ⅰ)/教育心理学

    2022.4 - Now   Institution:中央大学

  • Neuro- and Physiological Psychology

    2022.4 - Now   Institution:The Open University of Japan

  • 生理学(脊髄の体性機能、脳幹の体性機能、卵巣から分泌されるホルモン、女性生殖機能、医科行動科学概論、医科統計学概論)

    2012.4 - Now   Institution:横浜市立大学

  • 組織学総論実習

    2011.4 - Now   Institution:東邦大学

  • Physiology training

    2004.4 - Now   Institution:Yokohama City University

  • 生命科学特別講義Ⅳ

    2022.9 - 2022.10   Institution:北海道大学大学院

  • biology and neuroscience I

    2021.9 - 2022.3   Institution:Keio University

  • 行動科学概論(行動の心理学的理解 認知の情報処理、行動の心理学的理解 行動と個人の性格、行動の心理学的理解 行動の臨床心理学的測定、行動の心理学的理解 対人行動と社会的行動、行動と学習)

    2021.4 - 2022.3   Institution:自治医科大学大学院

  • 発達生物心理学研究Ⅰ/Ⅱ/Ⅲ/Ⅳ

    2017.6 - 2022.3   Institution:自治医科大学大学院

  • 発達生物心理科学演習Ⅰ/Ⅱ

    2017.6 - 2022.3   Institution:自治医科大学大学院

  • 2学年選択セミナー(心理アセスメント演習)

    2014.8 - 2022.3   Institution:自治医科大学

  • セミナー(今、知りたい心理学)

    2014.8 - 2022.3   Institution:自治医科大学

  • 臨床発達心理学

    2014.8 - 2022.3   Institution:自治医科大学

  • 心理アセスメント論

    2014.8 - 2022.3   Institution:自治医科大学

  • 社会心理学

    2014.8 - 2022.3   Institution:自治医科大学

  • 臨床心理学

    2014.8 - 2022.3   Institution:自治医科大学

  • 生物心理学

    2014.8 - 2022.3   Institution:自治医科大学

  • 理科総合

    2014.8 - 2022.3   Institution:自治医科大学

  • 人文科学総合講義(心と科学について考える)

    2014.8 - 2022.3   Institution:自治医科大学

  • 心理学概論

    2014.8 - 2022.3   Institution:自治医科大学

  • 人間学の話題

    2020.6 - 2021.6   Institution:大阪大学

  • 社会の中の心理学

    2016.11 - 2020.11   Institution:立命館大学

  • 行動科学特別講義

    2019.8 - 2019.9   Institution:首都大学東京大学院

  • 医学的理解‐行動障害・てんかん‐

    2018.1 - 2019.6   Institution:国立特別支援教育総合研究所

  • 大学院博士課程講義 共通選択科目 生体構造コース(組織学各論)

    2013.8 - 2014.7   Institution:東邦大学

  • 人体発生学(生殖腺の原基と分化、生殖管と外生殖器の原基と分化)

    2013.8 - 2014.7   Institution:東邦大学

  • 内分泌系(精巣・副生殖腺・精路の組織構造、卵巣・卵管・子宮の組織構造、視床下部・下垂体・松果体の組織・細胞構築、甲状腺・副甲状腺の組織・細胞構築、副腎・膵臓の組織・細胞構築)

    2013.8 - 2014.7   Institution:東邦大学

  • 血液・リンパ系(リンパ系組織の組織構築)

    2013.8 - 2014.7   Institution:東邦大学

  • 行動神経解剖学(心理解剖学)

    2011.4 - 2014.7   Institution:東邦大学

  • 先端医科学演習

    2011.4 - 2014.7   Institution:東邦大学

  • 基礎統合PBLテュートリアル

    2011.4 - 2014.7   Institution:東邦大学

  • 基礎統合実習(ミクロ形態)

    2011.4 - 2014.7   Institution:東邦大学

  • 生命科学入門(心と身体)

    2013.4 - 2014.3   Institution:東京医療学院大学

  • 心理統計学

    2011.4 - 2012.3   Institution:人間総合科学大学

  • 生物・衛生・生薬系統合演習(PBL)

    2008.4 - 2011.3   Institution:姫路獨協大学

  • 基礎実験(生物)

    2008.4 - 2011.3   Institution:姫路獨協大学

  • 生理学Ⅱ

    2008.4 - 2011.3   Institution:姫路獨協大学

  • 生理学実習

    2008.4 - 2011.3   Institution:姫路獨協大学

  • 動物心理学

    2006.4 - 2007.3   Institution:目白大学

  • 行動神経科学(生理心理学)

    2006.4 - 2007.3   Institution:目白大学

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Committee Memberships

  • 2023.1 - Now

    日本発達心理学会   発達心理学研究編集委員会編集委員  

  • 2022.4 - Now

    日本行動科学学会   地区別運営委員(関東・甲信越地区)  

  • 2022.4 - Now

    日本行動科学学会   編集委員会委員  

  • 2021.6 - Now

    日本心理学会   理事  

  • 2017.10 - Now

    日本学術会議   連携会員(心理学・教育学委員会 心の科学のキャリアパス構築分科会委員・心身の健康・適応に対する心理学的支援分科会委員(2023年12月 - 現在)/科学者委員会 男女共同参画分科会 性差に基づく科学技術イノベーションの検討小分科会幹事(2021年2月 - 2023年9月)/心理学・教育学委員会 心の研究将来構想分科会委員・社会のための心理学分科会委員・心理学教育プログラム検討分科会委員・公認心理師の専門性と社会貢献検討分科会委員(2020年12月 - 2023年9月)/科学的エビデンスに基づく「スポーツの価値」の普及の在り方に関する委員会幹事(2018年12月 - 2020年9月)/科学者委員会 研究評価分科会委員(2018年11月 - 2023年9月)/科学と社会委員会 科学と社会企画分科会委員(2018年9月 - 2020年9月)/心理学・教育学委員会 社会のための心理学分科会幹事(2018年4月 - 2020年9月)/心理学・教育学委員会 心の先端研究と心理学専門教育分科会委員(2018年2月 - 2020年9月))  

  • 2017.9 - Now

    日本心理学諸学会連合   心理学検定局運営委員  

  • 2017.3 - Now

    日本心理学会   地域別代議員(関東)  

  • 2016.4 - Now

    文部科学省 科学技術・学術政策研究所 科学技術予測センター   専門調査員  

  • 2017.3 - 2023.9

    日本学術会議   若手アカデミー構成員(運営分科会委員・イノベーションに向けた社会連携分科会委員長・GYA総会国内組織分科会委員(2020年12月 - 2023年9月)/幹事・運営分科会委員・イノベーションに向けた社会連携分科会副委員長・若手科学者ネットワーク分科会委員(2017年12月 - 2020年9月))  

  • 2018.4 - 2022.3

    日本行動科学学会   編集委員会委員長  

  • 2016.2 - 2022.3

    日本心理学会   認定心理士の会幹事会幹事  

  • 2017.10 - 2021.9

    日本心理学会   認定心理士の会運営委員会委員長  

  • 2015.11 - 2019.10

    日本心理学会   認定心理士資格認定委員会委員  

  • 2016.4 - 2018.6

    日本心理学会   若手の会幹事会幹事  

  • 2016.4 - 2018.3

    日本行動科学学会   広報委員会委員長  

  • 2013.4 - 2018.3

    日本行動科学学会   若手の会代表  

  • 2017.3 - 2017.9

    日本学術会議   特任連携会員  

  • 2013.5 - 2016.7

    第31回国際心理学会議 組織委員会   プログラム委員会委員  

  • 2015.4 - 2016.3

    文部科学省 科学技術政策研究所 科学技術動向研究センター   専門調査員  

  • 2014.11 - 2016.3

    日本心理学会   若手の会運営委員会委員  

  • 2012.4 - 2016.3

    日本行動科学学会   広報委員会委員  

  • 2013.4 - 2013.9

    日本行動計量学会   第41回大会実行委員会委員  

  • 2012.4 - 2012.9

    日本行動科学学会   2012年度年次大会委員会委員長  

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Social Activities

  • 未来社会創造シンポジウム

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    那須会議準備委員会  那須会議  2023.11    

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  • 未来の仕事「秋田に学ぶ過去~現在~未来」

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  • はちげんめっ!第57講

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  • 特集「日本学術会議の任命拒否問題から3年。学術会議若手アカデミーが掲げる課題と提案」

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  • 2040年の科学・学術と社会を見据えて取り組むべき10の課題~イノベーション・越境研究・地域連携・国際連携・人材育成・研究環境~

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    日本学術会議  学術フォーラム  2023.7    

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