EXPRESSION OF NR2B IN DIFFERENT BRAIN REGIONS AND EFFECT OF NR2B ANTAGONISM ON LEARNING DEFICITS AFTER EXPERIMENTAL SUBARACHNOID HEMORRHAGE
EXPRESSION OF NR2B IN DIFFERENT BRAIN REGIONS AND EFFECT OF NR2B ANTAGONISM ON LEARNING DEFICITS AFTER EXPERIMENTAL SUBARACHNOID HEMORRHAGE
复制标题
NR2B在不同脑区的表达及NR2B拮抗对实验性蛛网膜下腔出血后学习障碍的影响
DOI：
10.1016/j.neuroscience.2012.11.024
复制
发表时间：
2013-02-12
期刊：
影响因子：
3.3
通讯作者：
Wang, Z.
中科院分区：
文献类型：
--
作者：
Chen, G.;Li, Q.;Wang, Z.
大约50%的蛛网膜下腔出血（SAH）后存活的患者存在认知或神经行为功能障碍。其机制尚不清楚。NR 2B是N-甲基-D-天冬氨酸（NMDA）受体的亚单位之一，已被证明是突触功能和行为认知的重要因素。实验一旨在研究SAH后大鼠大脑皮层、海马和小脑中NR 2B表达的时程。在实验2中，我们评估了Ro 25-6981（一种特异性NR 2B拮抗剂）对SAH后学习缺陷和行为活动的调节作用。所有SAH动物在第0天接受一次自体血液注射到视交叉前池中。通过Western印迹分析和免疫组织化学评估NR 2B。在Morris水迷宫中研究认知和记忆的变化。结果表明，SAH组NR 2B表达较对照组明显降低，且在第1 ~ 3天达到最低点。免疫组织化学染色显示NR 2B主要表达于皮层、海马和小脑三个不同区域的神经元。腹腔注射Ro 25-6981后，SAH所致的学习障碍明显加重，临床行为评分也明显降低。我们的研究结果表明，NR 2B表达下调后，在实验性SAH和NR 2B拮抗剂导致SAH后认知功能障碍的发展增强。(c)2012年IBRO。由爱思唯尔有限公司出版。保留所有权利。
Approximately 50% of patients who survived after aneurysmal subarachnoid hemorrhage (SAH) have cognitive or neurobehavioral dysfunction. The mechanisms are not known. NR2B, one of the subunits of N-methyl-D-aspartate (NMDA) receptors, has been proved to be an important factor for synapse function and behavior cognition. Experiment 1 aimed to investigate the timecourse of the NR2B expression in the cortex, hippocampus, and cerebellum after SAH in rats. In experiment 2, we assessed the effect of Ro 25-6981 (a specific NR2B antagonist) on regulation of learning deficits and behavioral activity following SAH. All SAH animals were subjected to injection of autologous blood into the prechiasmatic cistern once on day 0. NR2B was assessed by Western blot analysis and immunohistochemistry. Cognitive and memory changes were investigated in the Morris water maze. As a result, the expression of NR2B was decreased remarkably in SAH groups compared with the control group and the low ebb was on days 1-3. The immunohistochemical staining demonstrated expression of NR2B was present mainly in the neurons in all of the three different regions, such as the cortex, hippocampus, and cerebellum. After Ro 25-6981 intraperitoneal administration, learning deficits induced by SAH was markedly aggravated and clinical behavior scale was also significantly decreased. Our results suggest that NR2B expression is down-regulated in the brain after experimental SAH and NR2B antagonism resulted in augmentation of the development of cognitive dysfunction after SAH. (c) 2012 IBRO. Published by Elsevier Ltd. All rights reserved.