Activation of NMDA receptors increases brain-derived neurotrophic factor (BDNF) mRNA expression in the hippocampal formation.

In the present study, it is demonstrated that activation of NMDA receptors upregulates brain-derived neurotrophic factor (BDNF) in granule cells of the dentate gyrus and CA3 pyramidal neurons. BDNF mRNA levels in the granule cells peaked within 4 h, were still evident at 24 h, and returned to control levels within 48 h. In the CA3 region, BDNF mRNA levels were significantly increased at 2 h, peaked at 4 h, and returned to control values by 8 h following NMDA treatment. Finally, the effects of NMDA on BDNF mRNA expression were blocked by AP5, an NMDA receptor antagonist. These findings provide evidence that the in vivo activation of NMDA receptors may regulate the expression of this neurotrophin.