Project/Area Number |
26460240
|
Research Category |
Grant-in-Aid for Scientific Research (C)
|
Allocation Type | Multi-year Fund |
Section | 一般 |
Research Field |
Medical pharmacy
|
Research Institution | Fujita Health University (2016) Meijo University (2014-2015) |
Principal Investigator |
|
Co-Investigator(Kenkyū-buntansha) |
野田 幸裕 名城大学, 薬学部, 教授 (90397464)
|
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
|
Project Status |
Completed (Fiscal Year 2016)
|
Budget Amount *help |
¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2016: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2014: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
|
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 / N-メチル-D-アスパルギン酸(NMDA)受容体 / 神経再生 / グルコルチコイド / モノアミン作動性神経 / 治療抵抗性 |
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.
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