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2016 Fiscal Year Final Research Report

Investigation in mechanism and therapeutic strategy into vulnerability to mood disorder after exposure to stress in the stage of neuro-development of mice

Research Project

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Project/Area Number 26460240
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Medical pharmacy
Research InstitutionFujita Health University (2016)
Meijo University (2014-2015)

Principal Investigator

Nabeshima Toshitaka  藤田保健衛生大学, 保健学研究科, 客員教授 (70076751)

Co-Investigator(Renkei-kenkyūsha) HIRAMATSU Masayuki  名城大学, 薬学部, 教授 (10189863)
Research Collaborator MOURI Akihiro  藤田保健衛生大学, 医療科学部, 准教授 (20597851)
YOSHIMI Akira  名城大学, 薬学部, 助教 (00637671)
HIDA Hirotake  名城大学, 大学院・薬学研究科, 研究員
HASEGAWA Sho  名城大学, 大学院・薬学研究科, 大学院生
MAMIYA Takayoshi  名城大学, 薬学部, 准教授 (70340297)
OZAKI Norio  名古屋大学, 大学院・医学系研究科, 教授 (40281480)
YAMADA Kiyofumi  名古屋大学, 大学院・医学系研究科, 教授 (30303639)
KITAGAKI Shinji  名城大学, 薬学部, 教授 (20281818)
Project Period (FY) 2014-04-01 – 2017-03-31
Keywords幼若期 / 社会的敗北ストレス / 遺伝子発現解析 / モノアミン作動性神経系 / グルタミン酸作動性神経系 / エピジェネティック制御機構
Outline of Final Research Achievements

The social behavioral impairment induced by social defeat stress exposure during juveniles was persistent to adult. The development of social impairment may be due to the suppression of neurogenesis via activation of glucocorticoid receptors (GR) induced by stress. The social defeat stress induced dysfunction of serotonergic and dopaminergic neuronal systems in the prefrontal cortex. The combined treatment of a dopamine receptor partial agonist with a selective serotonin reuptake inhibitor or a non-competitive N-methyl-D-aspartate receptor antagonist attenuated the social impairment. DNA microarray analysis revealed that the social defeat stress induced the changes of gene expression in the monoaminegic, glutamatergic neuronal systems, and epigenetic regulation. Juvenile mice are vulnerable to social defeat stress, and activation of GR, monoaminergic and/or glutamatergic neuronal dysfunctions due to changes in related-gene expressions were involved in the social impairment.

Free Research Field

神経精神薬理学

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Published: 2018-03-22  

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