Analysis of the mechanisms underlying increased histogenetic cell death in developing cerebellum of the hypothyroid rat: determination of the time required for granule cell death.

The connection between the date of formation of granule cells and their final position in the internal granular layer of the cerebellum has been described previously. In rats made hypothyroid since the end of gestation, the distribution of the pyknotic cells in the internal granular layer of the cerebellar cortex was also previously found to be age-related. In 14-day-old hypothyroid rats, it was compared with that of the granule cells which were labeled after a pulse of [3H]thymidine at various stages of development. It appeared that the localization of the dying cells corresponded roughly to that of granule cells labeled on day 9. Therefore the maximum time required for granule cell death was about 5 days. Since the migratory phase through the molecular layer lasted about two days, the granule cells died after a maximum time of 3 days following their deposition in the internal granular layer. Information concerning the time of survival of the dying granule cells was important for subsequent investigation of the mechanisms underlying increased granule cell death in the hypothyroid cerebellum and the corrective effects of thyroid hormone.