Repair of the external granular layer of the hamster cerebellum after prenatal and postnatal administration of methylazoxymethanol

Abstract

Abstract The purpose of this experiment was to examine the influence of methylazoxymethanol acetate (Mam ac) on cell proliferation and regeneration of the external granular layer in the cerebellum of the hamster. Pregnant hamsters were treated with 10 mg/kg/day Mam ac on days 13–15 of gestation and youngsters on the second, third, and fourth or fourth, fifth and sixth postnatal days. In animals treated during intrauterine life and examined on the day of birth a large number of cells in the external granular layer were destroyed, but some seemingly healthy ones always remained. In those permitted to live, surviving cells formed a new external granular layer and by the 20th postnatal day no morphological differences could be detected between the treated and control animals. In animals treated on the second to fourth postnatal days practically all the cells of the external granular layer were destroyed. By the tenth day the Purkinje cells were located throughout the molecular zone. Many of them showed a cytoplasmic cone extending centrally instead of toward the periphery. The internal granular layer contained only a few cells, apparently owing to failure of the normal inflow of neurons from the external granular layer. In animals treated on the fourth to sixth postnatal days most cells in the external granular layer were destroyed. During the following days surviving cells presumably gave rise to a new external granular layer. The cells of this layer failed to migrate centrally. Instead they remained located in the molecular layer where they formed an extra layer of cells, which had the appearance of granule cells. The animals were ataxic, although retinal abnormalities may have been partially responsible for the symptoms.