Molecular Research on Environmental Influence on Neuroplasticity and Neurogenesis

环境对神经可塑性和神经发生影响的分子研究

• 批准号: 13470195
• 负责人: KANBA Shigenobu
• 金额: $ 9.28万
• 依托单位: University of Yamanashi (2003)山梨医科大学 (2001-2002)
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2001
• 资助国家: 日本
• 起止时间: 2001 至 2003
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-13470195/
• 关键词: stress; environment; hippocampus; neurogenesis; nitric oxide; serotonin transporter; estrogen; prolactin releasing hormone; 神経再生; セロトニン; トランスポーター; インターロイキン; HSD; 学習; 不安; 母子分離ストレス; 扁桃体; 遺伝子; 神経伝達物質

Stress vulnerability is in part caused by long term influence from environment. Poor early environment is known to cause trait of anxiety and impaired cognitive function afterward. However, the precise mechanism is unknown. We decided to investigate the mechanism underlying long term influence by environment on brain development.We have carried our below stated research.1) By using twin methods, we determined contribution of genes and environments to development of personality. We found about 30-40% of our personality is determined by genes. Non-shared environment has strong contribution as compared to shared environment.2)Serotonin transporter gene is known to be associated with the trait of anxiety. We investigated association between the polymorphism of the gene and binding potential of transporter in vivo human brain that is measured by PET.3)We studied neurochemical functions of stress related chemicals such as nitric oxide, brain estrogen, prolactin releasing peptide, orexine, amyloid P component.We focused hippocampal functions in stress response and tried to answer to some questions below.1)How does environment stress impairs hippocampal functions including neurogenesis at molecular levels?2)How does Interferon that is know to cause depression clinically damage hippocampus?By understanding these mechanisms, what can we do to repair these aspects of pathology?

压力脆弱性部分是由环境的长期影响造成的。早期不良的环境会导致焦虑和认知功能受损。然而，确切的机制尚不清楚。我们决定研究环境对大脑发育的长期影响的机制。我们进行了以下研究。1）通过使用孪生方法，我们确定了基因和环境对人格发展的贡献。我们发现我们的性格大约有30-40%是由基因决定的。与共享环境相比，非共享环境具有更强的贡献。2）已知5-羟色胺转运体基因与焦虑性状相关。我们研究了基因多态性与PET测量的体内人脑转运蛋白结合潜力之间的关联。3）我们研究了应激相关化学物质如一氧化氮、脑雌激素、催乳素释放肽、食欲素、淀粉样蛋白P成分。我们重点关注海马在应激反应中的功能，并试图回答以下一些问题。1）环境应激如何在分子水平上损害海马神经发生等功能？2)干扰素是如何导致抑郁症的临床损害海马体？通过了解这些机制，我们可以做些什么来修复这些病理方面？

项目成果

Sugiyama, N., et al.: "Temporal changes in the expression of brain-derived neurotrophic factor mRNA in the ventromedial nucleus of the hypothalamus of the developing rat brain."Molecular Brain Research. 15. 69-77 (2002)

Sugiyama, N. 等人：“发育中的大鼠大脑下丘脑腹内侧核中脑源性神经营养因子 mRNA 表达的时间变化。”分子脑研究。

Ono Y, Ando J, Onoda N, Yoshimura K, Momose T, Hirano M, Kanba S: "Dimensions of temperament as vulnerability factors in depression."Moleculer Psychiatry. 7. 948-953 (2002)

Ono Y、Ando J、Onoda N、Yoshimura K、Momose T、Hirano M、Kanba S：“气质维度作为抑郁症的脆弱因素。”分子精神病学。

Ono, Y.: "Dimensions of temperament as vulnerability factors in depression"Molecular Psychiatry. 7. 948-953 (2002)

小野，Y.：“气质维度作为抑郁症的脆弱因素”分子精神病学。

Soma, M., et al.: "Mice lacking serum amyloid P component do not necessarily develop severe autoimmune disease."Biochem.Biophys.Res.Comm.. 286. 200-205 (2001)

Soma, M., 等人：“缺乏血清淀粉样蛋白 P 成分的小鼠不一定会患上严重的自身免疫性疾病。”Biochem.Biophys.Res.Comm.. 286. 200-205 (2001)

Soma, M., et al.: "Mice lacking serum amyloid P component do not necessarily develop severe autoimmune disease."Biochem.Biophys.Res.Com.. 286. 200-205 (2001)

Soma, M., 等人：“缺乏血清淀粉样蛋白 P 成分的小鼠不一定会患上严重的自身免疫性疾病。”Biochem.Biophys.Res.Com. 286. 200-205 (2001)