REGULATION OF NEUROPEPTIDES IN ADULT-RAT FOREBRAIN BY THE NEUROTROPHINS BDNF AND NGF

The expression of neuropeptides and neurotrophic factors is altered in the hippocampus after seizure induction in rats. Because the increase in brain-derived neurotrophic factor (BDNF) and nerve growth factor ( NGF) mRNAs precede changes in neuropeptide expression after seizure, i t is possible that BDNF and NGF mediate subsequent alterations in pept ide expression. To test this hypothesis directly, BDNF or NGF was infu sed into the hippocampus and cortex of adult rats. To ascertain the re gional specificity of any observed effects of neurotrophin administrat ion on neuropeptide expression, infusions into the striatum were also studied. To control for specificity, vehicle was also infused into the same sites. Peptide and mRNA alterations were assessed by Northern an alysis, immunohistochemistry and radioimmunoassay. BDNF produced eleva tions of peptide and mRNA for neuropeptide Y and cholecystokinin in hi ppocampus and cortex, and somatostatin in cortex. BDNF increased mRNAs for neuropeptide Y, cholecystokinin, substance P and dynorphin in str iatum. In contrast, BDNF decreased dynorphin peptide and mRNA in hippo campus. NGF's effects were limited to small mRNA increases, without co rresponding changes in peptide levels, for neuropeptide Y in hippocamp us and striatum, substance P in cortex and cholecystokinin in striatum . The distinct and limited effects of NGF infusion on neuropeptide exp ression demonstrate that BDNF's effects are not non-specific results o f protein infusion into the brain. These findings indicate that BDNF m ay play a regionally specific role in modulating neuropeptide expressi on in the normal brain as well as in various pathophysiological states .