Perinatal methylazoxymethanol acetate uncouples coincidence of orientation of cerebellar folia and parallel fibers

Perinatal administration of methylazoxymethanol acetate in the rat, as a one time injection on gestational day 21, postnatal days 0, 1 or 2, altered the parallel orientation of cerebellar folia. The effect persisted into adulthood. In animals injected on one of the postnatal days 3, 4 or 5, the folial pattern was not altered. Even when the injection was repeated for three days on postnatal days 3, 4 and 5, changes in the cerebellar surface were not found. However, in animals receiving a low protein diet during the last five days of gestation, the three injection regimen produced a distortion of the folial pattern. The surface of cerebella of animals injected on gestational day 21 through postnatal day 2 was covered with small blebs resembling the surface of a cauliflower head. In sagittal sections, islands of cortical laminae appeared to be isolated from the arbor vitae. However, serial reconstruction of the granular layer from sections revealed that these pieces were continuous with the arbor vitae. Surprisingly, cerebella having malaligned folia also had varying degrees of Purkinje cell somas distributed throughout the granule cell layer rather than in a single layer. This occurred even when the granule cell layer approached normal thickness. Analysis of cerebellar weight from the group injected on the day of birth revealed three levels of weight reduction: severe (greater than 40%), moderate (20-40%) and mild (less than 20%). The granule cell deficit was directly related to the weight reduction of the cerebella. In the severely-affected cerebella, areas of the cortex were virtually devoid of granule cells. The moderately-affected cerebella had a continuous granular layer which was thick and thin. In the mild type, the layer was relatively normal in thickness but, nevertheless, the cerebellar surface was highly distorted. In all animals treated with methylazoxymethanol acetate on days G21 through P5, parallel fibers were disoriented. This occurred even though the folia appeared normal in the G20, P3, P4, P5 and P3-5 injected groups. Bundles of parallel fibers crisscrossed in the plane of the cerebellar surface in all areas where a molecular layer was found.(ABSTRACT TRUNCATED AT 400 WORDS)