DIFFERENTIAL ACTIVATION OF MICROGLIA AND ASTROCYTES FOLLOWING TRIMETHYL TIN-INDUCED NEURODEGENERATION

We have investigated the response of astrocytes and microglia to trime thyl tin intoxication in the septum, hippocampus, olfactory bulb, and pyriform cortex of the rat. Microglia were studied qualitatively using lectin histochemistry, and astrocytes were examined both qualitativel y with immuno-histochemistry, and quantitatively using an immunoassay for glial fibrillary acidic protein. Our results show that activated m icroglia first appeared 2 days after trimethyl tin intoxication in the lateral septum acid hippocampus. Four days after trimethyl tin intoxi cation, the same regions revealed a most intense microglial reaction c haracterized by microglial hypertrophy and the formation of phagocytic clusters. By day 7, microglial activation in the septum and hippocamp us had lessened, suggesting that the cells were reverting to the resti ng phenotype. The microglial response in the pyriform cortex and olfac tory bulb, while being later in onset than in the septum and hippocamp us, showed a similar progression of microglial changes reaching maxima l intensity 7 days after trimethyl tin intoxication. Significant incre ases in the expression of glial fibrillary acidic protein were observe d in all regions examined and typically occurred after microglial acti vation was already underway. We conclude that microglial and astroglia l reactions which occur in response to trimethyl tin-induced neuronal necrosis are separated in time, with microglial activation preceding a strogliosis. In addition, our study stresses the importance of microgl ia as an endogenous source of CNS macrophages, and illustrates the mer it of histochemical analysis with microglial markers for the early del ineation of neurotoxicant-induced brain damage.