The synthesis of nerve growth factor and brain-derived neurotrophic factor in hippocampal and cortical neurons is regulated by specific transmitter systems

Abstract

Both nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) exert neurotrophic actions on the cholinergic neurons of the basal forebrain nuclei. These neurotrophic factors are synthesized by hippocampal and cortical neurons that are located in the projection field of the basal forebrain cholinergic neurons. Both in vivo and in vitro the levels of NGF- and BDNF-mRNAs are increased up to 20-fold by kainic acid via non-NMDA glutamate receptors. Enhancement of the effectiveness of the GABAergic system by benzodiazepam or direct GABA agonists blocks the effect of kainic acid and reduces the basic levels of NGF- and BDNF-mRNAs. Whereas the increases in both NGF- and BDNF-mRNAs above normal levels are mediated by non-NMDA receptors, maintenance of the normal levels of NGF- and BDNF-mRNAs seems to be mediated predominantly by NMDA receptors. The regulation of NGF and BDNF synthesis via specific transmitter systems is discussed in the context of the refined tuning of synaptic functions, the potential implications for memory functions, and the possible therapeutic consequences for the treatment of Alzheimer's disease.