Chronic ethanol exposure and withdrawal influence NMDA receptor subunit and splice variant mRNA expression in the rat cerebral cortex
Chronic ethanol exposure and withdrawal influence NMDA receptor subunit and splice variant mRNA expression in the rat cerebral cortex
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DOI：
10.1016/s0006-8993(98)01340-7
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发表时间：
1999-02-20
期刊：
影响因子：
2.9
通讯作者：
Wilce, PA
中科院分区：
文献类型：
--
作者：
Hardy, PA;Chen, WB;Wilce, PA
已知慢性乙醇暴露和随后的戒断可改变NMDA受体活性。本研究研究了慢性乙醇给药和停药对大鼠大脑皮层几种NMDA受体亚基和剪接变异mrna表达的影响。乙醇蒸气暴露诱导小鼠对乙醇依赖。为了描述戒断期间癫痫引起的表达变化与戒断本身引起的表达变化之间的关系，另一组幼年大鼠被注射戊四氮（PTZ） （30 mg/kg, i.p）。将长期治疗和停药的动物皮层的RNA样本与成对对照的动物的RNA样本进行比较。NMDA受体mRNA表达的变化是通过核糖核酸酶保护实验来确定的，该实验针对NR2A、-2B、-2C和NR1-pan亚基以及三个可选择剪接的NR1插入片段（NR1-pan描述了所有已知的NR1剪切变体，由5‘插入片段和两个3’插入片段产生）。含5′插入物与不含5′插入物的NR1 mRNA的比例在乙醇暴露期间和退出后48小时内都有所下降。NR2B mRNA的表达在暴露期间升高，但在停药后18小时恢复到对照水平。与成对喂养的对照组相比，乙醇处理组的NR2A、NR2C、NR1-pan和两个3' NR1插入mrna的水平没有改变。在ptz处理的动物中，未检测到任何NMDA受体亚基mRNA水平的变化。这些数据支持了一个假设，即NMDA受体亚基组成的变化可能是神经元对慢性乙醇抑制的适应的基础，因此可能在戒断过度活跃的沉淀中很重要。(C) 1999 Elsevier Science B.V.版权所有
Chronic ethanol exposure and subsequent withdrawal are known to change NMDA receptor activity. This study examined the effects of chronic ethanol administration and withdrawal on the expression of several NMDA receptor subunit and splice variant mRNAs in the rat cerebral cortex. Ethanol dependence was induced by ethanol vapour exposure. To delineate between seizure-induced changes in expression during withdrawal and those due to withdrawal per se, another group of naive rats was treated with pentylenetetrazol (PTZ) injection (30 mg/kg, i.p.). RNA samples from the cortices of chronically treated and withdrawing animals were compared to those from pairfed controls. Changes in NMDA receptor mRNA expression were determined using ribonuclease protection assays targetting the NR2A, -2B, -2C and NR1-pan subunits as well as the three alternatively spliced NR1 inserts (NR1-pan describes all the known NR1 splice variants generated from the 5' insert and the two 3' inserts). The ratio of NR1 mRNA incorporating the 5' insert vs, that lacking it was decreased during ethanol exposure and up to 48 h after withdrawal. NR2B mRNA expression was elevated during exposure, but returned to control levels 18 h after withdrawal. Levels of NR2A, NR2C, NR1-pan and both 3' NR1 insert mRNAs from the ethanol-treated groups did not alter compared with the pair-fed control group. No changes in the level of any NMDA receptor subunit mRNA was detected in the PTZ-treated animals. These data support the hypothesis that changes in NMDA receptor subunit composition may underlie a neuronal adaptation to the chronic ethanol-inhibition and may therefore be important in the precipitation of withdrawal hyperactivity. (C) 1999 Elsevier Science B.V. All rights reserved.