The effects of pre-natal exposure to methylazoxymethanol acetate on microglia.

The effects of exposure to a cytotoxic agent, methylazoxymethanol acetate (MAM Ac), on the distribution, density and quantitative morphology of microglia in the rat forebrain have been examined with the aid of a peroxidase-conjugated lectin derived from Griffonia simplicifolia. Following exposure to MAM Ac (25 mg/kg maternal body weight) on embryonic day 13 (E13), round microglia were concentrated around the areas of induced cell death at the outer margins of the ventricular germinal zone, particularly in the striatopallidal angle and dorsal thalamus. By E19, there were no detectable differences in microglia distribution between experimental and control animals. The increase in number of microglial cells in the neocortex and caudatoputamen on exposure to MAM Ac lasted for only 4 to 6 days. Subsequently, the number of microglia dropped below control values in both regions. The density of microglia in these areas was similar in control and experimental animals from 6 days after exposure. The proportion of microglia relative to all other cells was also similar at post-natal day 17 (P17) in both experimental and control animals. These results suggest that the distribution and final size of the microglial population is determined by the microenvironment and not by the extent of cell death which may have acted as the initial stimulus to microglial invasion.