Springer J E, Gwag B J, Sessler F M
Department of Neurology, Hahnemann University, Philadelphia, PA 19102.
Brain Res Mol Brain Res. 1994 Apr;23(1-2):135-43. doi: 10.1016/0169-328x(94)90219-4.
Nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) are two structurally-related neurotrophins synthesized in dentate gyrus granule cells and pyramidal neurons of the hippocampal formation. These neurons receive excitatory glutamatergic afferents from the entorhinal cortex via the angular bundle/perforant path. In the present study, we tested whether electrophysiological stimulation of this glutamatergic pathway modifies NGF or BDNF messenger RNA (mRNA) expression in vivo. Within hours following brief trains of high frequency angular bundle stimulation, the levels of mRNA encoding both neurotrophins were increased exclusively in granule cells of the ipsilateral dentate gyrus. The increase in neurotrophic factor mRNA expression was found to be mediated through the N-methyl-D-aspartate (NMDA) glutamate receptor subtype, and occurred in the absence of seizure. These findings provide evidence that neurotrophic factor mRNA levels in the hippocampal formation are increased by direct activation of excitatory afferents originating in the entorhinal cortex. We suggest that the function of some neurotrophin-responsive neuronal populations may depend upon the integrity and activity of neurons in the entorhinal cortex, a population of neurons reported to be compromised in patients with Alzheimer's disease.
神经生长因子（NGF）和脑源性神经营养因子（BDNF）是两种结构相关的神经营养因子，在齿状回颗粒细胞和海马结构的锥体细胞中合成。这些神经元通过角束/穿通通路从内嗅皮质接收兴奋性谷氨酸能传入纤维。在本研究中，我们测试了对该谷氨酸能通路的电生理刺激是否会在体内改变NGF或BDNF信使核糖核酸（mRNA）的表达。在高频角束刺激的短暂序列后的数小时内，编码这两种神经营养因子的mRNA水平仅在同侧齿状回的颗粒细胞中升高。发现神经营养因子mRNA表达的增加是通过N-甲基-D-天冬氨酸（NMDA）谷氨酸受体亚型介导的，并且在没有癫痫发作的情况下发生。这些发现提供了证据，表明起源于内嗅皮质的兴奋性传入纤维的直接激活会增加海马结构中的神经营养因子mRNA水平。我们认为，一些神经营养因子反应性神经元群体的功能可能取决于内嗅皮质中神经元的完整性和活性，据报道，阿尔茨海默病患者的这一群神经元会受损。
