Differential activation of microglia and astrocytes following trimethyl tin-induced neurodegeneration.
We have investigated the response of astrocytes and microglia to trimethyl 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 qualitatively with immunohistochemistry, and quantitatively using an immunoassay for glial fibrillary acidic protein. Our results show that activated microglia first appeared 2 days after trimethyl tin intoxication in the lateral septum and hippocampus. Four days after trimethyl tin intoxication, the same regions revealed a most intense microglial reaction characterized by microglial hypertrophy and the formation of phagocytic clusters. By day 7, microglial activation in the septum and hippocampus had lessened, suggesting that the cells were reverting to the resting phenotype. The microglial response in the pyriform cortex and olfactory bulb, while being later in onset than in the septum and hippocampus, showed a similar progression of microglial changes reaching maximal intensity 7 days after trimethyl tin intoxication. Significant increases in the expression of glial fibrillary acidic protein were observed in all regions examined and typically occurred after microglial activation was already underway. We conclude that microglial and astroglial reactions which occur in response to trimethyl tin-induced neuronal necrosis are separated in time, with microglial activation preceding astrogliosis. In addition, our study stresses the importance of microglia as an endogenous source of CNS macrophages, and illustrates the merit of histochemical analysis with microglial markers for the early delineation of neurotoxicant-induced brain damage.
McCann
M J
MJ
Procter and Gamble Company, Miami Valley Laboratories, Cincinnati, OH 45239, USA.
O'Callaghan
J P
JP
Martin
P M
PM
Bertram
T
T
Streit
W J
WJ
D000818:Animals; D001253:Astrocytes / Q000187:drug effects*; D001921:Brain / Q000166:cytology* / Q000187:drug effects; D004797:Enzyme-Linked Immunosorbent Assay; D005904:Glial Fibrillary Acidic Protein / Q000276:immunology / Q000378:metabolism; D006735:Horseradish Peroxidase; D007150:Immunohistochemistry; D008262:Macrophage Activation / Q000187:drug effects*; D008297:Male; D017628:Microglia / Q000187:drug effects*; D009410:Nerve Degeneration / Q000187:drug effects*; D051381:Rats; D014298:Trimethyltin Compounds / Q000633:toxicity*
D005904:Glial Fibrillary Acidic Protein; D014298:Trimethyltin Compounds; D006735:Horseradish Peroxidase