In utero radiation-induced changes in growth factor levels in the developing rat brain.

Abstract:

PURPOSE: To investigate the role of growth factors in the compensatory response to radiation injury during development of the brain. Levels of gene expression in the embryonic rat brain were assessed for IGF-I, IGF-II, BDNF and NT-3. MATERIALS AND METHODS: Pregnant Wistar rats were exposed to a single dose of 10, 20 or 40 cGy X-rays on day 15 or 17 of gestation. Animals were sacrificed 4 or 24 h after exposure. IGF-I, BDNF and NT-3 proteins were detected by immunocytochemistry, while IGF-I and IGF-II mRNA by in situ hybridization, and Northern analysis respectively. RESULTS: In utero low dose X-irradiation led to a decrease in IGF-I gene expression and a compensatory increase in the expression of IGF-II, BDNF and NT-3 in the developing rat brain. IGF-I, BDNF and NT-3 immunopositive cells were detected among proliferating, migratory and post-mitotic neurones in the developing neuroepithelium. CONCLUSIONS: Low dose prenatal irradiation of the developing brain results in down-regulation of IGF-I, which could lead to cell death by apoptosis. On the other hand, IGF-II, BDNF and NT-3 gene expression is increased following irradiation, possibly as a compensatory mechanism.