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Aging of the dog brain : molecular pathological study on the mechanism of biometal (iron) accumulation

狗脑衰老：生物金属（铁）积累机制的分子病理学研究

基本信息

批准号：
12833006
负责人：
SHIMADA Akinori
金额：
$ 2.3万
依托单位：
Tottori University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2000
资助国家：
日本
起止时间：
2000 至 2001
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-12833006/
关键词：
Dog Brain Aging Iron Metallothionein 8-OHdG 8-OHdG フェリチン

项目摘要

Purpose of the studyAge-related changes of the brain of dogs including neuronal degeneration induced by the free radical intoxication were pathologically studied. The study included relationship between the iron accumulation and neuronal degenerative changes and mechanism of the iron accumulation in the brain. 1. Distribution of the age-related morphological changes, accumulated iron (cell species, electron microscopic investigation), 2. Demonstration of iron-related proteins (ferritin, transferrin), 3. 8-OHdG and 4-HNE expression as a marker of cell injury induced by free radicals, 4. Metallothionein expression (immunohistochemical, biochemical analysis).Summarized findings and conclusion1. Iron accumulation was demonstrated in the cytoplasm of glial cells (oligodendroglia), some evidence of iron accumulation in the mitochondria.2. Ferritin distribution was similar to that of iron accumulation in the cytoplasm of glial cells ; ferritin immunoreactivity became strong with age.3. 8-OHdG and 4-HNE expression as a marker of cell injury induced by free radicals, increased with age suggesting that oxygen radicals would, in part, be responsible for brain aging.4. Level of total Metallothionein decreased with age in both gray and white matter, indicating that shortage of the anti-peroxidization protein would be, in part, responsible for the brain aging.

研究目的对犬脑组织的增龄性变化，包括自由基中毒所致的神经元变性进行病理学研究。本研究包括铁蓄积与神经元退行性改变的关系以及脑内铁蓄积的机制。2.铁相关蛋白(铁蛋白、转铁蛋白)、3.8-OHdG和4-HNE的表达作为自由基致细胞损伤的标志；4.金属硫蛋白的表达(免疫组织化学、生化分析)。结果：1.在胶质细胞(少突胶质细胞)的细胞质中发现了铁的积累，这是铁在线粒体中积累的一些证据。铁蛋白的分布与铁离子在胶质细胞胞浆中的积聚相似；铁蛋白免疫反应随着年龄的增长而增强。8-OHdG和4-HNE的表达作为自由基诱导的细胞损伤的标志，随着年龄的增长而增加，这表明氧自由基可能在一定程度上与脑老化有关。脑灰质和白质中总金属硫蛋白水平均随年龄增长而下降，提示抗过氧化蛋白的缺乏可能是导致脑老化的部分原因。