In vivo mechanism of neuronal injury by DRP1

DRP1损伤神经元的体内机制

• 批准号: 22590956
• 负责人: SHIINO Akihiko
• 金额: $ 2.83万
• 依托单位: Shiga University of Medical Science
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2010
• 资助国家: 日本
• 起止时间: 2010 至 2012
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-22590956/
• 关键词: 臨床神経生理学; アルツハイマー病; ミトコンドリア; アミロイドβ; 磁気共鳴; ダイナミン様蛋白; 一酸化窒素; 酸化ストレス; 軸索障害

The purpose of our study was to clarify whether S-nitrosylation induced excessive mitochondrial fission and fragmentation in the brain. We stereotactically administered glyceryl trinitrate in the mouse brain of both triple transgenic (3xTg) and wild type (Wt) mice, and measured SNO-Drp1 by biotin switch assay and compared mitochondrial morphology by deconvolution fluorescence microscopy using mito-DsRed2 staining. SNO-Drp1 formation was increased in a dose-dependent manner induced by glyceryl trinitrate, and this phenomenon was more prominent in 3xTg than in Wt mice. Mito-DsRed2 staining showed excessive mitochondrial fission and fragmentation in the brain of 3xTg but not prominently in the brain of Wt mice. These results suggest that β-amyloid may cause excessive mitochondrial fragmentation and mitochondrial dysfunction by induction of excessive SNO-Drp1 production.

我们研究的目的是阐明s -亚硝基化是否会导致大脑中线粒体过度分裂和断裂。我们立体定向给药三硝酸甘油在三转基因（3xTg）和野生型（Wt）小鼠的大脑中，用生物素开关法测定SNO-Drp1，用mito-DsRed2染色用反卷积荧光显微镜比较线粒体形态。三硝酸甘油诱导SNO-Drp1的形成呈剂量依赖性增加，这种现象在3xTg小鼠中比在Wt小鼠中更为明显。Mito-DsRed2染色显示3xTg小鼠脑内线粒体分裂和断裂过多，而Wt小鼠脑内线粒体分裂和断裂不明显。这些结果表明β-淀粉样蛋白可能通过诱导过量的SNO-Drp1产生导致线粒体过度断裂和线粒体功能障碍。

项目成果

分子標的MR造影剤の開発(総説)

分子靶向 MR 造影剂的开发（综述）

• 发表时间: 2010
• 期刊: 日本分子イメージング学会機関誌
• 作者: 椎野顯彦;犬伏俊郎
• 通讯作者: 犬伏俊郎

Hippocampal metabolites and memory performances in patients with amnestic mild cognitive impairment and Alzheimer’s disease

• DOI: 10.1016/j.nlm.2012.01.006
• 发表时间: 2012-03
• 期刊: Neurobiology of Learning and Memory
• 影响因子: 2.7
• 作者: Toshiyuki Watanabe;A. Shiino;I. Akiguchi

Absolute Quantification in Proton Magnetic Resonance Spectroscopy Is Useful to Differentiate Amnesic Mild Cognitive Impairment from Alzheimer’s Disease and Healthy Aging

• DOI: 10.1159/000318750
• 发表时间: 2010-06
• 期刊: Dementia and Geriatric Cognitive Disorders
• 影响因子: 2.4
• 作者: Toshiyuki Watanabe;A. Shiino;I. Akiguchi

Mapping of cerebral metabolic rate of oxygen using DSC and BOLD MR imaging: a preliminary study.

使用 DSC 和 BOLD MR 成像绘制大脑氧代谢率图：初步研究。

• 发表时间: 2012
• 期刊: Magn Reson Med Sci.
• 作者: M. Nagai;T. Torimoto;T. Miyamoto;T. Kawashima;T. Shibata;Shiino A
• 通讯作者: Shiino A

脳萎縮解析のためのプログラム開発(BAAD)

脑萎缩分析（BAAD）程序开发

• 发表时间: 2011
• 作者: 椎野顯彦;渡辺俊之;白樫義友;秋口一郎;遠山育夫;犬伏俊郎
• 通讯作者: 犬伏俊郎