Defect of the cerebellar vermis induced by prenatal gamma-ray irradiation in radiosensitive BALB/c mice

The developing fetal brain is one of the most susceptible organs to irradiation insult. Prenatal irradiation-induced abnormalities in the cerebrum have been well examined in mouse fetuses. However, little information on abnormalities in the cerebellum caused by irradiation is available. Moreover, few reports have examined the chronological changes of the brain from the prenatal to the postnatal period. To analyze the chronological changes induced by irradiation, we exposed pregnant mice to gamma-ray irradiation on embryonic day 13.5 (E13.5) and investigated the histopathology of the cerebellum at several time points from E14.5 to postnatal day 28. BALB/cA mice were used, which is a radiosensitive strain, and C57BL/6J, which is a radioresistant strain. The irradiated BALB/c showed a remarkable vermis deficit after birth, and histological analysis demonstrated that there were severe losses of the external germinal layer (EGL) and Purkinke cell layer. TUNEL analysis shoed that apoptosis was strongly induce in the cerebellar anlage of the irradiated BALB/c compared to the C57BL/6J at E14.5. Immunohistochemical analysis revealed a significant decrease of phospho-histone H3 positive EGL cells in the irradiated BALB/c at E18.5 and E0, indicating that irradiation causes a decrease in the number of mitotic cells. The results suggest that the strong induction of apoptosis in radiosensitive BALB/c led to a decrease of proliferation activity in the cerebellar anlage during embryonic development, and consequently, severe cerebellar abnormality was evoked.