BRAIN-DERIVED NEUROTROPHIC FACTOR AND NEUROTROPHIN-4 INCREASE NEUROTROPHIN-3 EXPRESSION IN THE RAT HIPPOCAMPUS

Hippocampal levels of mRNA encoding nerve growth factor (NGF) and brai n-derived neurotrophic factor (BDNF) are rapidly induced by enhanced n euronal activity following seizures and glutamate or muscarinic recept or activation. However, the levels of neurotrophin-3 (NT-3) mRNA acute ly decrease after limbic seizures suggesting that a different mode of regulation may exist for these neurotrophins. Here we show that BDNF a nd neurotrophin-4 (NT-4), but not NT-3 itself, up-regulate NT-3 mRNA i n cultured hippocampal neurons. In the rat hippocampus, the muscarinic receptor agonist, pilocarpine increased BDNF mRNA levels rapidly and those of NT-3 with a delay of several hours. Injection of BDNF into ne onatal rats elevated NT-3 mRNA in the hippocampus which demonstrates t hat BDNF is able to enhance NT-3 expression in vivo. The regulation of NT-3 by BDNF and NT-4 enlargens the neurotrophic spectrum of these ne urotrophins to include neuron populations responsive primarily to NT-3 .