GAP-43 MESSENGER-RNA EXPRESSION IN THE DEVELOPING RAT-BRAIN - ALTERATIONS FOLLOWING LEAD-ACETATE EXPOSURE

The developmental neurotoxicity of environmental lead exposure manifes ts as alterations in neural functioning and perturbed axonal and dendr itic development. To examine the hypothesis that such lead-induced alt erations in the neural network are associated with an altered mRNA exp ression of a specific neural cell growth associated protein, mRNA leve ls of GAP-43 (growth associated protein 43) were measured in the corte x and hippocampus of developing Long-Evans hooded rats following vario us lead exposure paradigms. Postnatal developmental profiles (PND 6, 9 , 12, 15, 20, and 25) of mRNA expression were generated following eith er prenatal (gestational day 13 to birth), postnatal(postnatal day I t o postnatal day 20), or perinatal (gestational day 13 to postnatal day 20) exposure to lead acetate (0.2% in the drinking water of the dam). In control rats, GAP-43 mRNA levels displayed a distinct developmenta lly regulated profile of expression in both the cortex and hippocampus , characterized by an elevated level of expression within the first we ek of life. This peak level of expression was significantly depressed following either postnatal or perinatal exposure to lead acetate, whil e prenatal lead exposure produced an initial elevation of GAP-43 mRNA on postnatal day 6 followed by a sharp decline. These data suggest tha t lead exposure results in altered mRNA expression of a specific neura l cell growth associated protein critical to the normal process of dev elopment, This perturbation in expression may play a role in the previ ously reported effects of lead acetate on axonal elongation during dev elopment of the nervous system and the subsequent alteration in nervou s system functioning. (C) 1996 Inter Press, Inc.