KAKEYAMA, Masaki

写真a

Affiliation

Faculty of Human Sciences, School of Human Sciences

Job title

Professor

Homepage URL

http://www.waseda.jp/sem-lbn/index.html

Concurrent Post 【 display / non-display

  • Affiliated organization   Global Education Center

  • Faculty of Human Sciences   Graduate School of Human Sciences

  • Faculty of Human Sciences   School of Human Sciences (Online Degree Program)

Education 【 display / non-display

  • 1992.04
    -
    1995.03

    Waseda University   Graduate School of Human Sciences   Department of Life Sciences  

Degree 【 display / non-display

  • Waseda University   Ph.D.

Professional Memberships 【 display / non-display

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    Japan Society of Endocrine Disrupters Research

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    The Japanese Society of Toxicology

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    The Japanese Society for Hygiene

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    the Japanese Society of Biological Psychiatry

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    The Japanese Society of Neuropsychopharmacology

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Research Interests 【 display / non-display

  • Behavioral Neuroscience

  • Preventive Medical Science

  • Environmental Brain Science

Papers 【 display / non-display

  • Neurochemical evidence for differential effects of acute and repeated oxytocin administration

    Seico Benner, Yuta Aoki, Takamitsu Watanabe, Nozomi Endo, Osamu Abe, Miho Kuroda, Hitoshi Kuwabara, Yuki Kawakubo, Hidemasa Takao, Akira Kunimatsu, Kiyoto Kasai, Haruhiko Bito, Masaki Kakeyama, Hidenori Yamasue

    Molecular Psychiatry   Sep 27   doi: 10.1038/s413 - (IF=11.640)  2018  [Refereed]

     View Summary

    © 2018, Springer Nature Limited. A discrepancy in oxytocin’s behavioral effects between acute and repeated administrations indicates distinct underlying neurobiological mechanisms. The current study employed a combination of human clinical trial and animal study to compare neurochemical changes induced by acute and repeated oxytocin administrations. Human study analyzed medial prefrontal metabolite levels by using 1H-magnetic resonance spectroscopy, a secondary outcome in our randomized, double-blind, placebo-controlled crossover trial of 6 weeks intranasal administrations of oxytocin (48 IU/day) and placebo within-subject design in 17 psychotropic-free high-functioning men with autism spectrum disorder. Medial prefrontal transcript expression levels were analyzed in adult male C57BL/6J mice after intraperitoneal injection of oxytocin or saline either once (200 ng/100 μL/mouse, n = 12) or for 14 consecutive days (200 ng/100 μL/mouse/day, n = 16). As the results, repeated administration of oxytocin significantly decreased the medial prefrontal N-acetylaspartate (NAA; p = 0.043) and glutamate–glutamine levels (Glx; p = 0.001), unlike the acute oxytocin. The decreases were inversely and specifically associated (r = 0.680, p = 0.004 for NAA; r = 0.491, p = 0.053 for Glx) with oxytocin-induced improvements of medial prefrontal functional MRI activity during a social judgment task not with changes during placebo administrations. In wild-type mice, we found that repeated oxytocin administration reduced medial frontal transcript expression of N-methyl-d-aspartate receptor type 2B (p = 0.018), unlike the acute oxytocin, which instead changed the transcript expression associated with oxytocin (p = 0.0004) and neural activity (p = 0.0002). The present findings suggest that the unique sensitivity of the glutamatergic system to repeated oxytocin administration may explain the differential behavioral effects of oxytocin between acute and repeated administration.

    DOI

  • 高次脳機能の健康を阻害する幼少期の環境要因と遺伝要因.

    掛山正心

    日本衛生学雑誌   73   110-114  2018  [Refereed]  [Invited]

    DOI

  • マウスにおける自閉スペクトラム発現の行動指標

    掛山正心, ベナー聖子, 藤原昌也

    日本生物学的精神医学会誌   29   103-108  2018  [Invited]

  • Excessive activation of AhR signaling disrupts neuronal migration in the hippocampal CA1 region in the developing mouse.

    Kimura E, Kubo KI, Endo T, Nakajima K, Kakeyama M, Tohyama C

    J Toxicol Sci.   4   25-30 - (IF=1.719)  2017  [Refereed]

    DOI

  • Association of impaired neuronal migration with cognitive deficits in extremely preterm infants.

    Kubo KI, Deguchi K, Nagai T, Ito Y, Yoshida K, Endo T, Benner S, Shan W, Kitazawa A, Aramaki M, Ishii K, Shin M, Matsunaga Y, Hayashi K, Kakeyama M, Tohyama C, Tanaka KF, Tanaka K, Takashima S, Nakayama M, Itoh M, Hirata Y, Antalffy B, Armstrong DD, Yamada K, Inoue K, Nakajima K

    JCI Insight   2 ( 10 ) pii: 88609, (IF=13.251)  2017  [Refereed]  [International journal]

     View Summary

    Many extremely preterm infants (born before 28 gestational weeks [GWs]) develop cognitive impairment in later life, although the underlying pathogenesis is not yet completely understood. Our examinations of the developing human neocortex confirmed that neuronal migration continues beyond 23 GWs, the gestational week at which extremely preterm infants have live births. We observed larger numbers of ectopic neurons in the white matter of the neocortex in human extremely preterm infants with brain injury and hypothesized that altered neuronal migration may be associated with cognitive impairment in later life. To confirm whether preterm brain injury affects neuronal migration, we produced brain damage in mouse embryos by occluding the maternal uterine arteries. The mice showed delayed neuronal migration, ectopic neurons in the white matter, altered neuronal alignment, and abnormal corticocortical axonal wiring. Similar to human extremely preterm infants with brain injury, the surviving mice exhibited cognitive deficits. Activation of the affected medial prefrontal cortices of the surviving mice improved working memory deficits, indicating that decreased neuronal activity caused the cognitive deficits. These findings suggest that altered neuronal migration altered by brain injury might contribute to the subsequent development of cognitive impairment in extremely preterm infants.

    DOI PubMed

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Awards 【 display / non-display

  • Encouragement Award of Japanese Society for Hygiene

    2012.03  

  • VASEDA VNIVERSITAS PALMA IN MEMORIAM AZVSAONO

    1992.03  

Research Projects 【 display / non-display

  • Microscopic analysis based on the quantitative behavioral tests in rodents for identification of the molecular target of developmental neurotoxicity

    Project Year :

    2009
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    2013
     

     View Summary

    The aim of this study is to develop the microscopic analysis methodology, and identify the molecular marker for developmental neurotoxicity of environmental chemicals. We found that perinatal exposure to a low dose of dioxin induces abnormal behaviors, including behavioral inflexibility, compulsive repetitive behavior, and low social dominance in mice. Immuhohistochemical analysis validated that hypoactivation of the medial prefrontal cortex (mPFC) and hyperactivation of the amygdala are the potential biological basis for these behavioral abnormalities.

  • Elucidation of developmental neurotoxicity mechanisms of polycyclic aromatic hydrocarbons via aryl hydrocarbon receptor

    Project Year :

    2009
    -
    2011
     

     View Summary

    Polyaromatic hydrocarbons(PAHs) are accumulated in the environment, and humans are exposed to them via food and environmental media. The objective of the present study is to elucidate possible effects and toxicity mechanisms of gestational exposure to PAHs in mice using behavioral tests. As a result, aryl hydrocarbon receptor itself was suggested to play a responsible role in the behavioral abnormality. The possible biological significance of this receptor in the brain function warrants future studies.

  • The profiling of gene expression evoked by co-exposure to dioxin and polychlorinated biphenyl.

    Project Year :

    2003
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    2006
     

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    Dioxin and its related compounds that are under administrative regulation are comprised of a group of compounds of dioxins, dibenzofurans and coplanar PCBs because they exert toxicities in an arylhydrocarbon (AhR)-dependent manner, as typically shown by 2,3,7,8-TCDD, the most toxic congener among this group compounds. In reality, humans are exposed to these compounds in combination from the environment, but possible health effects and the mechanism of toxicities exposed combinations of these congeners are largely unknown. In the present study, we exposed laboratory rodents to TCDD and PCB in combination, studied dose-response relationship of AhR-dependent and independent toxicities and carried out gene profiling analysis to provide information on the toxicity mechanism on a molecular basis. The new observations we found are five-fold. First, a very low dose of TCDD alone (50 ng/kg b.w., p.o.) significantly decreased learning performance. Second, neurobehavioral effects of a low dose of PCB126 (500 ng/kg b.w., the dose of which is equivalent to 50 ng TEQ/kg b.w.) decreased the learning performance. Third, dams that were administered PCB153 orally at a dose of 2.0 mg/kg b.w. on GD15

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Specific Research 【 display / non-display

  • マウス社会的競争環境課題の最適化

    2018  

     View Summary

    自閉スペクトラム関連症状を想定してマウス実験で広く用いられている行動テストを概観し、また我々の新たな行動テストについても触れながら、マウスの行動表現型や行動指標が精神医学上、はたしてヒトに外挿できるかどうかについて検討した。そして、マウスの意識レベルでの行動柔軟性を定量化する行動テスト、競争状態でマウスがみせる行動パターンを定量化する行動テストの最適化を行った。本研究の成果をもとに、2019年度AMED革新脳プロジェクトに採択された。

  • ダイオキシン毒性に基づく社会行動異常マーカーの同定

    2018  

     View Summary

    成人には影響の顕れない低用量の化学物質曝露が子どもの精神神経発達に影響を及ぼすという懸念が高まる中、環境脳科学研究室では、ダイオキシン類は自閉スペクトラム症(ASD)当事者に類似の精神神経発達の異常を引き起こすことを明らかにしてきた。 本研究では、曝露動物とヒトASD当事者の比較解析により、低用量ダイオキシンの胎児期・授乳期曝露によって生じる「社会行動異常」の血液中バイオマーカーの解析を行った。この成果をもとに、科研費挑戦的研究(開拓)に申請を行った。

  • 神経活動と行動表現型による神経毒性評価

    2018  

     View Summary

    これまでに動物実験により、残留性有機汚染物質(POPs)は極めて低用量で精神神経発達に影響を及ぼすことを明らかにしてきた。本研究では、動物行動試験のヒトへの外挿性の向上を目指し、自ら開発した自動行動試験にリアルタイム神経活動解析の実装を行なった。課題遂行中の行動と神経活動の変化を自動取得し、行動と神経活動の定量データを客観的に結びつけることが期待される。本研究をもとに、2019年度科研費基盤研究(A)に採択された。

  • 競争環境における「個性スペクトラム」の分子神経基盤

    2017  

     View Summary

    マウスなどの社会行動試験では1ないし2匹の刺激マウスを提示し、被験マウスの解析を行うといった限定的な解析が大多数を占めており、社会的個性やそのスペクトラムの生物学的基盤に関する研究は極めて乏しい。そこで我々はこれまでに、IntelliCage全自動行動解析システムを用い、14~16匹のマウスを集団生活させた状態で水飲み場を取り合わせるという、いわば「椅子取りゲーム」をマウスで行う社会的競争課題を開発した。本研究では、この社会的競争環境課題における行動成績と神経活動との対応について検討し、競争環境課題に関わる脳領域について明らかにすることができた。

  • 向社会性ハタネズミの表情識別能力の検証

    2017  

     View Summary

    我々は小動物用のTouch Screen型の視覚学習装置を新たに作製した。この装置を用いることで、例えば「K」と「M」の二つの図形を提示し、正解の図形を選ばせるといった図形弁別課題において、マウスは約1週間で90%超の正答率を示すことができる。本研究では、 voleにおける試験系を確立した。表情や個体を視覚刺激として用いることで、視覚刺激に対して反応し報酬をうるという課題を1時間に数百回行うようvoleをトレーニングし、視覚能力について調べることができた。

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Syllabus 【 display / non-display

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