Brain-derived neurotrophic factor and neurotrophin-4 increase neurotrophin-3 expression in the rat hippocampus

Abstract Hippocampal levels of mRNA encoding nerve growth factor (NGF) and brain‐derived neurotrophic factor (BDNF) are rapidly induced by enhanced neuronal activity following seizures and glutamate or muscarinic receptor activation. However, the levels of neurotrophin‐3 (NT‐3) mRNA acutely decrease after limbic seizures suggesting that a different mode of regulation may exist for these neurotrophins. Here we show that BDNF and neurotrophin‐4 (NT‐4), but not NT‐3 itself, up‐regulate NT‐3 mRNA in 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 neonatal rats elevated NT‐3 mRNA in the hippocampus which demonstrates that 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 neurotrophins to include neuron populations responsive primarily to NT‐3.