BDNF regulates the expression and traffic of NMDA receptors in cultured hippocampal neurons
BDNF regulates the expression and traffic of NMDA receptors in cultured hippocampal neurons
复制标题
DOI：
10.1016/j.mcn.2007.02.019
复制
发表时间：
2007-06-01
影响因子：
3.5
通讯作者：
Duarte, Carlos B.
中科院分区：
文献类型：
--
作者：
Caldeira, Margarida V.;Melo, Carlos V.;Duarte, Carlos B.
神经营养因子BDNF调节CNS中突触强度的活性依赖性修饰。生理和生化证据表明NMDA谷氨酸受体是BDNF调节的靶点之一。在本研究中，我们研究了BDNF对培养的海马神经元NMDA受体亚单位的表达和质膜丰度的影响。急性刺激海马神经元BDNF差异上调NR1，NR2A和NR2B NMDA受体亚单位的蛋白水平，通过一种机制敏感的转录和翻译抑制剂。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NR2A和NR2B亚基的蛋白水平，但对NR1亚基没有影响。BDNF刺激30 min和24 h后，海马神经元胞膜上的NRI、NR2A和NR2B蛋白表达均不同程度增加。质膜相关NMDA受体亚单位的快速上调与NMDA受体活性的增加相关。结果表明，BDNF增加NMDA受体的丰度和它们向质膜的递送，从而上调培养的海马神经元中的受体活性。(c)2007爱思唯尔公司All rights reserved.
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 NRI, 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. (c) 2007 Elsevier Inc. All rights reserved.