Elucidation of pathophysiology of refractory depression and development of newer treatment based on the disturbance of spine dynamics

阐明难治性抑郁症的病理生理学并开发基于脊柱动力学紊乱的新疗法

• 批准号: 20591368
• 负责人: MORINOBU Shigeru
• 金额: $ 2.91万
• 依托单位: Hiroshima University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2008
• 资助国家: 日本
• 起止时间: 2008 至 2010
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-20591368/
• 关键词: 難治性うつ病; 脳由来神経栄養因子; 樹状突起スパイン; マイクロRNA; 海馬; 母子分離; 学習性無力; trkB受容体; BDNF; MeCP2; miR-132; miR-30a; miR-141; miR-200a; IMK-1; microRNA; スパイン; うつ病; LIMK-1

The present study was undertaken to examine whether the decreased synaptic density through the spine abnormality in the hippocampus is involved in the pathophysiology of refractory depression. We developed a rat model of refractory depression using neonatal isolation and learned helplessness. The principal findings of this study were that 1) the spine length of dendritic spines was longer in the hippocampus of the model rats without any changes in spine density, 2) the immunoreactivity of brain-derived neurotrophic factor (BDNF) was decreased, 3) the levels of microRNA (miR)-132 were decreased, 4) the levels of miR-134 were not affected, 5) the immunoreactivity of TrkB was decreased. These findings suggested that the spine abnormality due to the decreased BDNF-TrkB signal in the hippocampus may be involved in the pathophysiology of refractory depression, with less contribution by downregulation of BDNF through miR regulation from the 3' region of the BDNF gene.

本研究旨在探讨海马棘突异常引起的突触密度降低是否与难治性抑郁症的病理生理有关。我们利用新生儿隔离和习得性无助建立了难治性抑郁症大鼠模型。本研究的主要发现是：1）模型大鼠海马中树突棘的棘长度增加，棘密度无任何变化，2）脑源性神经营养因子（BDNF）的免疫反应性降低，3）microRNA（miR）-132水平降低，4）miR-134水平不受影响，5）TrkB免疫反应性降低。这些发现表明，由于海马中BDNF-TrkB信号降低而导致的脊柱异常可能参与难治性抑郁症的病理生理学，通过来自BDNF基因3'区域的miR调节下调BDNF的贡献较小。

项目成果

Alteration in the hippocampal glycinergic system in an animal model of posttraumatic stress disorder.

创伤后应激障碍动物模型中海马甘氨酸系统的改变。

• 发表时间: 2010
• 期刊: J Psychiatric Res 44
• 作者: Yamamoto Shigeto;Morinobu Shigeru;Iwamoto Yasuyuki;Ueda Yuto;Takei Shiro;Fujita Yosuke;Yamawaki Shigeto
• 通讯作者: Yamawaki Shigeto

Neonatal isolation as an animal model of vulnerability for depression

新生儿隔离作为易患抑郁症的动物模型

• 发表时间: 2009
• 作者: Yamada M;Takahashi K;Ukai W;Hashimoto E;Saito T;Yamada. M.;Morinobu S
• 通讯作者: Morinobu S

うつ病発症感受性と養育環境

容易患抑郁症和养育环境

• 发表时间: 2008
• 作者: 森信繁;倉田明子;淵上学;松木文;土岐茂;山脇成人
• 通讯作者: 山脇成人

ストレスとうつ病動物モデル

压力和抑郁动物模型

• 发表时间: 2010
• 期刊: 別冊・医学のあゆみ
• 作者: 森信繁;高橋輝道;山本茂人
• 通讯作者: 山本茂人

栄養因子・成長因子とシナプス可塑性からみたうつ病の病態メカニズム

从营养因素、生长因子、突触可塑性角度探讨抑郁症的病理机制

• 发表时间: 2009
• 期刊: 精神神経学誌 111
• 作者: Fuchikami M;Morinobu S;Kurata A;Yamamoto S;Yamawaki S;尹浩信;Kurata A;尹浩信;森信繁
• 通讯作者: 森信繁