EFFECTS OF X-IRRADIATION ON NERVE GROWTH-FACTOR IN THE DEVELOPING MOUSE-BRAIN

The involvement of neurotrophins after radiation injury during brain d evelopment were studied in pregnant mice (C 57/B1) exposed on gestatio n day 15 to X-ray doses of 0.02-2 Gy. Nerve growth factor protein (NGF ) and different cholinergic markers were investigated on postnatal day I (PI) and day 21 (P21); in situ hybridization with brain-derived neu rotrophic factor (BDNF) and trkC (receptor serving to bind neurotrophi n-3) probes was investigated on P21 in cortex, hippocampus, septum and cerebellum. The level of NGF protein was increased in irradiated fore brain on P1 in a dose-related manner. However, on P21 the NGF protein dropped down below the control levels in irradiated hippocampus and ce rebellum. The response of acetylcholine esterase (AChE) activity in ce rebellum at P21 was correlated with the changes in the amount of NGF. The intensity of cell labelling with trkC probe decreased after irradi ation in the region of the hippocampus at P21, especially in dentate g yrus. The expression of BDNF mRNA was increased at P21 by low doses of irradiation (0.02-1 Gy) but was decreased by a high dose (2 Gy) in th e same area. Thus, the radiation induced an alteration of neurotrophin s, and the changes varied depending on the dose or time after irradiat ion. Such alterations in the pattern of growth factor production may m odulate the response of cells to radiation. Furthermore, NGF protein l evels and the expression of BDNF and trkC mRNA were affected by radiat ion doses as low as 0.02 Gy, indicating that during development the ne urotrophins and their receptors are very sensitive to radiation. Copyr ight (C) 1997 Elsevier Science Ireland Ltd.