Modulation of stretch-induced enhancement of neuronal NMDA receptor current by mGluR1 depends upon presence of glia
Modulation of stretch-induced enhancement of neuronal NMDA receptor current by mGluR1 depends upon presence of glia
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DOI：
10.1089/089771503770802907
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发表时间：
2003-11-01
影响因子：
4.2
通讯作者：
Faden, AI
中科院分区：
文献类型：
--
作者：
Lea, PM;Custer, SJ;Faden, AI
培养的神经元的拉伸已被用于模拟与脑创伤相关的弥漫性轴索损伤。N-甲基-D-天冬氨酸受体（NMDAR）活化和I组代谢型谷氨酸受体（mGluR）涉及这种损伤的病理生理学。在这里，我们详细的培养条件和mGluR 1调制的影响拉伸增强NMDA受体的活性，并显示存在的mGluR 1除了mGluR 5在神经胶质细胞。在无（PN）或有（NG）胶质细胞单层的皮质神经元中，牵张损伤（5.7 mm）通过增加最大NMDAR电流、降低电压依赖性Mg 2+阻滞和改变这些受体的动力学行为来增强NMDAR活性。在PN培养物中，mGluR 1的激活增加了拉伸增强的NMDAR活性，而在NG培养物中，这种活性降低。相反，在PN培养物中抑制mGluR 1限制了拉伸增强的NMDAR活性，而在NG培养物中活性增加。MGluR 1通过多种机制调节牵张增强的NMDAR活性，包括：改变峰值或稳态电流，影响NMDAR的Mg 2+阻断，或通过改变NMDAR动力学。神经胶质细胞的存在显着改变的性质mGluR 1介导的调制NMDAR活性和牵张诱导的损伤。总之，这些数据表明神经胶质mGluR 1和神经元NMDA受体活性之间的显着的神经元/神经胶质相互作用。
Stretching of cultured neurons has been used to model diffuse axonal injury associated with brain trauma. N-Methyl-D-aspartate receptor (NMDAR) activation and group I metabotropic glutamate receptors (mGluRs) are implicated in the pathophysiology of such injury. Here we detail the effects of culture condition and mGluR1 modulation on stretch-enhanced NMDA receptor activity, and show the presence of mGluR1 in addition to mGluR5 in glia. In cortical neurons grown in the absence (PN) or presence (NG) of a glial monolayer, stretch injury (5.7 mm) enhances NMDAR activity by increasing maximal NMDAR current, decreasing the voltage-dependent Mg2+ block, and altering the kinetic behavior of these receptors. In PN cultures, activation of mGluR1 increases stretch-enhanced NMDAR activity, whereas in NG cultures, such activity is reduced. In contrast, inhibition of mGluR1 in PN cultures limits stretch-enhanced NMDAR activity, whereas in NG cultures activity is increased. MGluR1 modulate stretch-enhanced NMDAR activity through multiple mechanisms including: altering peak or steady state current, affecting Mg2+ blockade of the NMDAR, or by changing NMDAR kinetics. The presence of glia significantly alters the nature of mGluR1-mediated modulation of NMDAR activity and stretch-induced injury. Together these data indicate a significant neuronal/glial interaction between glial mGluR1 and neuronal NMDA receptor activity.