Effects of low-dose X-irradiation on the development of the mouse cerebellar cortex

We labeled proliferating cells of the cerebellum of 6-day-old mice with 5-bromo-2'-deoxyuridine (BrdU) followed by a single exposure to 0.5, 1 or 2 Gy of X-rays. We then studied the effects of low-dose irradiation on the migration and survival of granule neurons in the mouse cerebellum. The animals were killed at 4 days, or at 2, 4 or 6 weeks after irradiation. Brains were fixed and BrdU-labeled cells in the cerebella were immunohistochemically analyzed. BrdU was predominantly distributed in the superficial layer of the external granular layer soon after injection. Four days after irradiation with 0.5 or 1 Gy, labeled cells were mainly seen in the inner granular layer, which was also the case in non-irradiated mice. However, following 2 Gy irradiation BrdU was found not only in the inner granular layer, but also in the Purkinje cell layer. This distribution was also seen at 2 and 4-6 weeks after irradiation. In animals irradiated with 1 Gy 4-6 weeks after irradiation, the proportion of labeled cells present in the inner granular layer decreased, while labeled cells in the Purkinje cell layer increased. On the other hand, 0.5 Gy irradiation did not change the distribution of labeled cells, except that the proportion of labeled cells in the inner granular layer decreased at 2 weeks after irradiation. The number of labeled cells in the cerebellar cortex per unit area decreased with time and dose. These results suggest that 2 Gy irradiation induces a migratory delay, abnormal distribution, and cell death of the granule neurons of the mouse cerebellum.