Summary
Graded degrees of micrencephaly were produced in the progeny of rats given 0, 14, 22, or 30 mg methylazoxymethanol acetate (MAM Ac) per Kg b.wt. on gestation day (GD) 15. Brains of animals from five litters were examined at each dose level. Golgi-Cox-stained sections prepared from brains of progeny of rats given 25 mg MAM Ac/kg on GD 15 were also evaluated for four micrencephalic and four control animals. Each increase in dosage of MAM Ac resulted in significantly greater loss in brain weight in the progeny. The largest effect was on the telencephalon. In the low dose group the telencephalon, though noticeably smaller, was structurally normal. The two higher doses resulted in easily visualized neuropathologic lesions in both the cerebral cortex and hippocampus. The external layers of the cerebral cortex were most severely affected. Layers V and VI were much better preserved but measurements on pyramidal cells in layer VI in the Golgi-Cox-stained sections showed them to have significantly fewer dendrites and spines than the normal animals. In addition to an intrinsic disorganization of the neocortex, periventricular nodular heterotopias and hippocampal ectopias were common. All the structural anomalies were most severe at the highest dose, though they were also readily apparent at the intermediate dose. The findings suggest to us that MAM Ac treatment during gestation not only produces an acute lesion resulting in the destruction of many proliferating neuroblasts, but that many of the surviving neuroblasts may sustain a chronic lesion altering their subsequent development.
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Dambska, M., Haddad, R., Kozlowski, P.B. et al. Telencephalic cytoarchitectonics in the brains of rats with graded degrees of micrencephaly. Acta Neuropathol 58, 203–209 (1982). https://doi.org/10.1007/BF00690802
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DOI: https://doi.org/10.1007/BF00690802