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Licensed Unlicensed Requires Authentication Published by De Gruyter October 11, 2014

NMDA receptor activity determines neuronal fate: location or number?

  • Xianju Zhou EMAIL logo , Zhouyou Chen , Wenwei Yun and Hongbing Wang

Abstract

It is widely believed that the proper activation of N-methyl-D-aspartate (NMDA) receptors (NMDARs) promotes neuronal survival, whereas an excessive activation of NMDARs leads to neuronal damage. NMDARs are found at both synaptic and extrasynaptic sites. One current prevailing theory proposes the dichotomy of NMDAR activity. The role of the two population receptors is mutual antagonism. The activation of synaptic NMDARs, such as synaptic activity at physiological levels, promotes neuronal survival. However, the activation of extrasynaptic NMDARs occurring during stroke, brain injury, and chronic neurological diseases contributes to neuronal death. Thus, the location of NMDARs determines the neuronal fate. However, the theory is greatly challenged. Several studies suggested that synaptic NMDARs are involved in neuronal death. Recently, our work further showed that the coactivation of synaptic and extrasynaptic NMDARs contributes to neuronal death under neuronal insults. Therefore, we propose that the magnitude and duration of NMDAR activation determines the neuronal fate. More interestingly, there appears to be some subtle differences in the affinity between synaptic and extrasynaptic NMDARs, shedding light on the development of selective drugs to block extrasynaptic NMDARs.


Corresponding author: Xianju Zhou, Department of Neurology, Laboratory of Neurological Diseases, Changzhou No.2 People’s Hospital, the affiliated Hospital of Nanjing Medical University, 29 Xinglong Alley, Changzhou 213003, Jiangsu, China, e-mail:

Acknowledgments

This study was supported by the Science and Technology Developmental Key Project of Nanjing Medical University (2013NJU212 to X.Z.), Changzhou Applied Basic Research Program (CJ20130023 to Z.C.), National Institutes of Health (NIH) grants (MH093445 and NS072668 to H.W.), and American Heart Association postdoctoral fellowship (10POST4550000 to X.Z.).

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Received: 2014-7-30
Accepted: 2014-9-5
Published Online: 2014-10-11
Published in Print: 2015-2-1

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