Interplay between glutamate and gamma-aminobutyric acid transmitter systems in the physiological regulation of brain-derived neurotrophic factor and nerve growth factor synthesis in hippocampal neurons.

In the central nervous system brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) are predominantly located in neurons. Here we demonstrate that the balance between the activity of the glutamatergic and gamma-aminobutyric acid (GABA)ergic systems controls the physiological levels of BDNF and NGF mRNAs in hippocampal neurons in vitro and in vivo. The blockade of the glutamate receptors and/or stimulation of the GABAergic system reduces BDNF and NGF mRNAs in hippocampus and NGF protein in hippocampus and septum. The reduction of NGF in the septum reflects the diminished availability of NGF in the projection field of NGF-dependent septal cholinergic neurons. These neurons do not synthesize NGF themselves but accumulate it by retrograde axonal transport. The refined and rapid regulation of BDNF and NGF synthesis by the glutamate and GABA transmitter systems suggests that BDNF and NGF might be involved in activity-dependent synaptic plasticity. IMAGES:

在中枢神经系统（central nervous system）中，脑源性神经营养因子（brain-derived neurotrophic factor, BDNF）与神经生长因子（nerve growth factor, NGF）主要定位于神经元内。本研究证实，谷氨酸能系统与γ-氨基丁酸（gamma-aminobutyric acid, GABA）能系统的活性平衡，可在体外（in vitro）及体内（in vivo）条件下，调控海马神经元内BDNF与NGF的mRNA生理表达水平。阻断谷氨酸受体（glutamate receptors）或联合激活GABA能系统，均可降低海马组织以及隔区（septum）中的NGF蛋白含量，以及BDNF与NGF的mRNA水平。隔区内NGF水平的下调，反映了依赖NGF的隔区胆碱能神经元（cholinergic neurons）投射野（projection field）中NGF的可利用性降低；此类神经元自身无法合成NGF，而是通过逆向轴突运输（retrograde axonal transport）摄取NGF。谷氨酸与GABA递质系统对BDNF与NGF合成的精准且快速的调控作用，提示BDNF与NGF可能参与活性依赖的突触可塑性（activity-dependent synaptic plasticity）过程。图像：