Selective ablation of neurons by methylazoxymethanol during pre- and postnatal brain development.

Neonatal or pregnant albino rats were injected with either single or double doses of methylazoxymethanol (20 mg/kg) to test the temporal specificity of its effect on clearly definable regions of the brain. A single dose, to dams from gestational day 11 to 21 (G11-G21) and to neonatal rats from birth to postnatal day 5 (P0-P5), produced differential weight reductions among various brain regions. Two prominent peaks of reduction were found: one occurring between G13 and G15 for the cerebrum and hippocampus and one occurring between P0 and P1 for the cerebellum and olfactory bulbs. Dual injections of the drug on G14 and G15 produced 60% weight reduction in the cerebrum, and slightly earlier injections on G13 and G14 reduced the weight of the cerebellum by about 23%. This weight reduction was accompanied by narrowing of the cerebellar width, which we believe was due to fewer Purkinje cells. Dual injections of methylazoxymethanol at P0 and P1 reduced the weight of the olfactory bulb by 65%, the cerebellum by 62%, and the hippocampus by 18%. These results show that its short action is within the window of cell division for various neurons and becomes additive on two successive days. This precise toxic effect on brain development can be used to disproportionally reduce the number of neuroblasts in specific regions of the brain. A differential ablation allows analysis of plasticity on pyramidal and nonpyramidal cells of the neocortex and hippocampus, Purkinje and granule cells of the cerebellum, and the granule and mitral cells of the olfactory bulbs.