Department of Neurobiology, Key Laboratory of Medical Neurobiology of Ministry of Health of China, Zhejiang University School of Medicine, Hangzhou, Zhejiang, PR China.
J Affect Disord. 2013 Jul;149(1-3):422-5. doi: 10.1016/j.jad.2012.12.003. Epub 2013 Jan 10.
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.
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.
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.
The samples were relatively small and the depression group had used antidepressants.
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.
γ-氨基丁酸（GABA）是一种主要的抑制性神经递质。它可减弱下丘脑-垂体-肾上腺（HPA）轴的活性，而后者在抑郁症的发病机制中起着重要作用。本研究旨在确定抑郁症下丘脑室旁核（PVN）中的 GABA 能传入，并探讨其与促肾上腺皮质激素释放激素（CRH）神经元活性的相关性。
我们对 9 名重度抑郁症（MDD）和 5 名双相抑郁症（BD）患者以及 12 名匹配对照者的尸检下丘脑 PVN 中的谷氨酸脱羧酶（GAD）（65/67）-免疫反应性（ir）的密度进行了定量分析，此前一项研究已确定了这些对照者的 CRH 表达神经元数量。
MDD 患者的 PVN 中 GAD（65/67）-ir 的密度显著降低了 43%（P=0.028），BD 患者的 GAD（65/67）-ir 的密度则降低了 20%，但无统计学意义。此外，在抑郁症组中，GAD（65/67）-ir 的密度与 PVN 中 CRH-ir 神经元的数量之间存在显著的负相关（Rho=-0.527，P=0.032），但在对照组中则无此相关性。
样本相对较小，且抑郁症组曾使用过抗抑郁药。
PVN 中 GABA 能传入的减少可能导致 CRH-ir 神经元在抑郁症中的激活，在 MDD 中最为明显，这为这些患者使用 GABA 能激动剂提供了依据。
