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

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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.