Chronic stress regulates levels of mRNA transcripts encoding β subunits of the GABAA receptor in the rat stress axis
Chronic stress regulates levels of mRNA transcripts encoding β subunits of the GABAA receptor in the rat stress axis
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DOI：
10.1016/s0006-8993(00)03000-6
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发表时间：
2000-12-22
期刊：
影响因子：
2.9
通讯作者：
Wolfe, TJ
中科院分区：
文献类型：
--
作者：
Cullinan, WE;Wolfe, TJ
采用半定量杂交组织化学方法检测慢性非习惯性应激大鼠下丘脑室旁核(PVN)和海马区GABA(A)受体β1-3亚单位基因转录水平。在按随机顺序给予一系列应激源3周后，发现GABA(A)受体的pi亚单位在内侧微小细胞室旁核(MpPVN)的表达水平比对照组动物降低了48.3%。慢性应激后mpPVN的β2基因表达水平降低(29.8%)，CA(1)和CA(3)区BUR增加(分别为33.9%和23.2%)，齿状回BUR增加(24%)。这些结果表明，GABA(A)受体亚单位的组成可能在一个关键的调节部位发生改变，这可能对了解GABA能抑制对下丘脑-垂体-肾上腺皮质(HPA)轴的影响具有重要意义。促肾上腺皮质激素释放激素(CRH)神经元是糖皮质激素对应激刺激反应的最终共同途径的起源，GABA能传入参与了这些神经元的传入控制。调节这些部位的GABA(A)受体可能会改变对应激轴的主要抑制影响的效果，从而调节应激诱导的糖皮质激素分泌。(C)2000 Elsevier Science B.V.保留所有权利。
Semi-quantitative hybridization histochemical analyses were undertaken to determine expression levels of mRNA transcripts encoding the beta1-3 subunits of the GABA(A) receptor within the rat hypothalamic paraventricular nucleus (PVN) and hippocampal formation following exposure to a chronic non-habituating stress protocol. After delivery of a battery of stressors on a randomized schedule over a 3-week period, expression levels of the pi subunit of the GABA(A) receptor were found to be decreased in the medial parvocellular PVN (mpPVN) by 48.3% relative to control animals. Levels of beta2 mRNA following chronic stress were also found to be decreased in the mpPVN (29.8%), bur increased in hippocampal subfields CA(1) and CA(3) (33.9 and 23.2%, respectively) and increased (24%) in the dentate gyrus. The results suggest that GABA(A) receptor subunit composition may be altered at a key regulatory site, and may have important implications for studies aimed at understanding GABAergic inhibitory influences upon the hypothalamic-pituitary-adreno-cortical (HPA) axis. Hypophysiotropic CRH neurons serve as the origin of the final common pathway for glucocorticoid secretion in response to stressful stimuli, and GABAergic afferents have been implicated in afferent control of these neurons. Regulation of GABA(A) receptors at these sites may alter the efficacy of a major inhibitory influence upon the stress axis, and thereby modulate stress-induced glucocorticoid secretion. (C) 2000 Elsevier Science B.V. All rights reserved.