Reduced GAD65/67 immunoreactivity in the hypothalamic paraventricular nucleus in depression: A postmortem study
Reduced GAD65/67 immunoreactivity in the hypothalamic paraventricular nucleus in depression: A postmortem study
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DOI：
10.1016/j.jad.2012.12.003
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发表时间：
2013-07-01
影响因子：
6.6
通讯作者：
Bao, Ai-Min
中科院分区：
文献类型：
--
作者：
Gao, Shang-Feng;Klomp, Anne;Bao, Ai-Min
背景：γ-氨基丁酸（GABA）是一种主要的抑制性神经递质。它降低了下丘脑-垂体-肾上腺（HPA）轴的活性，HPA轴在抑郁症的发病机制中起着重要作用。本研究旨在探讨抑郁症下丘脑室旁核（PVN）GABA能神经元的传入及其与促肾上腺皮质激素释放激素（CRH）神经元活动的关系。对9例重性抑郁症（MDD）和5例双相抑郁症（BD）患者的下丘脑室旁核（PVN）谷氨酸脱羧酶（GAD）（65/67）免疫反应性（ir）密度进行了定量测定，结果：MDD患者室旁核GAD阳性神经元（65/67）-ir密度显著降低43%（P=0.028），而BD患者室旁核GAD阳性神经元密度无显著性降低20%（P=0.028）。此外，抑郁症组下丘脑室旁核GAD（65/67）免疫阳性神经元密度与CRH免疫阳性神经元数呈显著负相关（Rho =-0.527，P =0.032），而对照组没有。局限性：样本相对较小，抑郁症组曾使用抗抑郁药。减少GABA能输入PVN可能有助于激活CRH-ir神经元抑郁症，最突出的是在MDD，这提供了一个理由，为这些患者的GABA能激动剂处方。(C)2012爱思唯尔有限公司版权所有。
Background: Gamma-aminobutyric acid (GABA) is a major inhibitory neurotransmitter. It diminishes the activity of the hypothalamo-pituitary-adrenal (HPA) axis, which plays an important role in the pathogenesis of depression. The present study aimed at determining GABAergic input in the hypothalamic paraventricular nucleus (PVN) in depression and its correlation with the activity of corticotropin-releasing hormone (CRH) neurons.Methods: The density of glutamic acid decarboxylase (GAD)(65/67)-immunoreactivity (ir) was quantified in the postmortem hypothalamic PVN of 9 major depressive (MDD) and 5 bipolar depressive (BD) patients, together with 12 matched controls, whose CRH-expressing neuron numbers had been determined in a previous study.Results: There was a 43% significant reduction of the density of GAD(65/67)-ir in the PVN in MDD (P=0.028) and a 20% non-significant decrease in BD patients. In addition, there was a significant negative correlation between the density of GAD(65/67)-ir and the number of CRH-ir neurons in the PVN in the depression group (Rho = -0.527, P=0.032), but not in the control group.Limitations: The samples were relatively small and the depression group had used antidepressants.Conclusion: A diminished GABAergic input to the PVN may contribute to the activation of CRH-ir neurons in depression, most prominently in MDD, which provides a rationale for prescribing GABAergic agonists for these patients. (C) 2012 Elsevier B.V. All rights reserved.