Effects of thyroid dysfunction on the development of the rat cerebellum, with special reference to cell death within the internal granular layer.

The increased cell death within the internal granular layer of the cerebellar cortex, previously demonstrated by other investigators in 12-day-old rats treated with propylthiouracil, was found again in 10-, 14- and 21-day-old similarly treated young rats. In thyroid-deficient as well as in normal animals, cell death was maximal at 10 days. In hypothyroid rats, the greatest difference with the normal animals was at 14 days, when there was an increase by a factor of 20 of the number of dying cells. On day 13, the ratio of free to total N-acetyl-beta-D-glucosaminidase activities was also increased by 34%. Cell death predominantly occurred in the lower part of the internal granular layer at 10 days, in the middle part at 14 days and the upper part at 21 days. The increase in thickness of the molecular layer, which reflects the development of the Purkinje cell dendritic arborizations, was also more retarded than the acquisition of a normal ratio of granule cells to Purkinje cells. Administration of a daily dose of 0.10 mug thyroxine to thyroid-deficient animals was sufficient (and a lower dose insufficient) to return to normal the number of dying cells as well as the development of the molecular layer and the evolution of the ratio of granule cells to Purkinje cells. A daily dose of T4 as low as 0.20 or 0.25 mug already induced a marked hyperthyroid state resulting in a decrease in granule cells formation without increased cell death. Indeed, an increased cell death seemed to occur only when the normal synchronism between the development of the Purkinje cell arborizations and the laying down of granule cells was suppressed, as is the case in thyroid deficiency but not in neonatal hyperthyroidism.