Central administration of the excitotoxin N-methyl-D-aspartate increases nerve growth factor mRNA in vivo

N-methyl-D-aspartate (NMDA) receptor activation in the hippocampal formation is thought to play an important role in learning and memory. This limbic structure contains one of the highest concentrations of NMDA binding sites in the brain. The hippocampal formation also contains high levels of nerve growth factor (NGF) mRNA and protein in the central nervous system. The expression of this neurotrophic factor may be regulated by events involving glutamatergic neurotransmission. In the present study, in situ hybridization histochemistry was used to determine the effects of NMDA receptor activation on NGF mRNA expression in the hippocampal formation. The gene encoding this neurotrophic factor was increased exclusively in the granule cells of the dentate gyrus, a hippocampal structure that receives extensive glutamatergic innervation from the entorhinal cortex. It is suggested that one consequence of glutamatergic neurotransmission in the dentate gyrus is the activation of NGF mRNA. The increased expression of this neurotrophic factor may ultimately influence the function of NGF-responsive cells innervating the hippocampal formation.