A study on a novel therapeutic strategy for Alzheimer's disease Using neurosteroids.

使用神经类固醇治疗阿尔茨海默病的新策略的研究。

• 批准号: 24659259
• 负责人: SOKABE Masahiro
• 金额: $ 2.41万
• 依托单位: Nagoya University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Challenging Exploratory Research
• 财政年份: 2012
• 资助国家: 日本
• 起止时间: 2012-04-01 至 2014-03-31
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-24659259/
• 关键词: アルツハイマー病; アミロイドβ; 神経ステロイド; PREGS; 治療法開発; 海馬; 長期増強; アセチルコリン受容体

The aim of this study was to test whether the neurosteroids PREGS and DEHA improve the survival rate and function of newborn hippocampal granule cells in the dentate gyrus (DG), which are crucial for learning and memory, by using Alzheimer's disease (AD) model mice. Each mouse was given a daily subcutaneous injection of PREGS or DHEA at a dose of 20 mg/kg for a month, and morphological development of newborn granule cells in the DG was examined for 20 days from the day 20 after the first injection. Both agents largely improved the morphological development of new born cells, but only PREGS facilitated the synaptogenesis of newborn cells to preexisting neural circuits and contributed to the final survival rate of newborn granule cells. It is strongly suggested that PREGS can be a promising therapeutic drug for AD.

本研究旨在通过阿尔茨海默病（AD）模型小鼠，检测神经类固醇PREGS和DEHA是否能提高新生海马齿状回（DG）中对学习和记忆至关重要的颗粒细胞的存活率和功能。每只小鼠每天皮下注射PREGS或DHEA，剂量为20 mg/kg，连续1个月，从第一次注射后第20天起，观察DG新生颗粒细胞形态学发育。这两种药物都极大地改善了新生细胞的形态发育，但只有PREGS促进了新生细胞与预先存在的神经回路的突触发生，并对新生颗粒细胞的最终存活率有贡献。这表明，PREGS可能是一种很有前途的治疗AD的药物。

项目成果

Time-window of progesterone neuroprotection after stroke and its underlying molecular mechanisms. In"Advances in the Preclinical Study of Ischemic Stroke", (Ed. Balestrino M )

中风后黄体酮神经保护的时间窗及其潜在分子机制。

• 发表时间: 2012
• 作者: Cai W;Sokabe M;Chen L.
• 通讯作者: Chen L.

Differential effects of lipids and lyso-lipids on the mechanosensitivity of MscL and MscS

脂质和溶血脂质对 MscL 和 MScS 机械敏感性的不同影响

• 发表时间: 2012
• 期刊: PNAS
• 作者: Nomura T;Cranfield CG;Deplazes E;Owen DM;Macmillan A;Battle AR;Constantine M;Sokabe M;Martinac B
• 通讯作者: Martinac B

メカノバイオロジーからみた発がんと転移

机械生物学视角下的癌发生和转移

• 发表时间: 2013
• 作者: Xu Y;Tanaka M;Chen L;Sokabe M;Sokabr M.;Sokabe M.;Sokabe M.;Sokabe M.;曽我部正博
• 通讯作者: 曽我部正博

Mechanotransduction by cytoskeleton-regulated MS channels at cell-substrate adhesions

细胞骨架调节的 MS 通道在细胞-基质粘附方面的力转导

• 发表时间: 2014
• 作者: Xu Y;Tanaka M;Chen L;Sokabe M;Sokabr M.;Sokabe M.;Sokabe M.
• 通讯作者: Sokabe M.

InTech, Time-window of progesterone neuroprotection after stroke and its underlying molecular mechanisms

InTech，中风后黄体酮神经保护的时间窗及其潜在分子机制

• 发表时间: 2012
• 作者: Cai W;Sokabe M;Chen L,
• 通讯作者: Chen L,