Caldeira Margarida V, Melo Carlos V, Pereira Daniela B, Carvalho Ricardo F, Carvalho Ana Luísa, Duarte Carlos B
Center for Neuroscience and Cell Biology, Department of Zoology, University of Coimbra, 3004-517 Coimbra, Portugal.
Mol Cell Neurosci. 2007 Jun;35(2):208-19. doi: 10.1016/j.mcn.2007.02.019. Epub 2007 Mar 3.
The neurotrophin BDNF regulates the activity-dependent modifications of synaptic strength in the CNS. Physiological and biochemical evidences implicate the NMDA glutamate receptor as one of the targets for BDNF modulation. In the present study, we investigated the effect of BDNF on the expression and plasma membrane abundance of NMDA receptor subunits in cultured hippocampal neurons. Acute stimulation of hippocampal neurons with BDNF differentially upregulated the protein levels of the NR1, NR2A and NR2B NMDA receptor subunits, by a mechanism sensitive to transcription and translation inhibitors. Accordingly, BDNF also increased the mRNA levels for NR1, NR2A and NR2B subunits. The neurotrophin NT3 also upregulated the protein levels of NR2A and NR2B subunits, but was without effect on the NR1 subunit. The amount of NR1, NR2A and NR2B proteins associated with the plasma membrane of hippocampal neurons was differentially increased by BDNF stimulation for 30 min or 24 h. The rapid upregulation of plasma membrane-associated NMDA receptor subunits was correlated with an increase in NMDA receptor activity. The results indicate that BDNF increases the abundance of NMDA receptors and their delivery to the plasma membrane, thereby upregulating receptor activity in cultured hippocampal neurons.
神经营养因子脑源性神经营因子（BDNF）调节中枢神经系统中依赖活动的突触强度修饰。生理和生化证据表明N-甲基-D-天冬氨酸（NMDA）谷氨酸受体是BDNF调节的靶点之一。在本研究中，我们调查了BDNF对培养的海马神经元中NMDA受体亚基的表达和质膜丰度的影响。用BDNF急性刺激海马神经元，通过一种对转录和翻译抑制剂敏感的机制，差异性地上调了NR1、NR2A和NR2B NMDA受体亚基的蛋白质水平。相应地，BDNF也增加了NR1、NR2A和NR2B亚基的mRNA水平。神经营养因子NT3也上调了NR2A和NR2B亚基的蛋白质水平，但对NR1亚基没有影响。BDNF刺激30分钟或24小时后，与海马神经元质膜相关的NR1、NR2A和NR2B蛋白量差异性增加。质膜相关NMDA受体亚基的快速上调与NMDA受体活性的增加相关。结果表明，BDNF增加了NMDA受体的丰度及其向质膜的转运，从而上调了培养的海马神经元中的受体活性。
