Department of Neuropsychiatry, College of Medicine and Institute of Mental Health, Hanyang University, Seoul, Republic of Korea.
Eur Neuropsychopharmacol. 2012 May;22(5):330-8. doi: 10.1016/j.euroneuro.2011.09.001. Epub 2011 Oct 2.
Human post-mortem brain studies have revealed reduced density and size of neurons and glial cells in the dorsolateral prefrontal cortex (dlPFC) in major depressive disorder (MDD). However, the basis of these cytoarchitectural abnormalities and the relationship between them are not understood. We hypothesized that the reduced density of GABAergic neurons and glial cells was associated with altered glutamate neurotransmission in the dlPFC. In order to test this hypothesis, we examined a specific marker type (i.e., calretinin, CR: as a marker of GABAergic neurons) and also attempted to identify the neuropathological markers that correlate with the density of CR-immunoreactive (IR) GABAergic neurons in the dlPFC, using the Stanley Neuropathology Consortium Integrative Database (SNCID, http://sncid.stanleyresearch.org/), which is a web-based tool used to integrate Stanley Medical Research Institute (SMRI) data sets. We found that the density of CR-IR GABAergic neurons was significantly lower in layer I of the dlPFC of MDD patients (n=15) than in that of unaffected controls (n=15) (p=0.021). CR-IR GABAergic neuronal changes were positively correlated with changes in several markers for glial cells and pyramidal neurons in the dlPFC of all SNC subjects (n=60). We also found that the glutamate changes negatively correlated with glial fibrillary acidic protein (GFAP) expression levels and CR-IR GABAergic neuronal density in the prefrontal cortex of all SNC subjects (P<0.05). These findings yield some insight into the mechanism by which increased glutamatergic neurotransmission leads to excitotoxic damage both in neurons and glial cells in the dlPFC of MDD patients.
人类死后大脑研究表明，在重度抑郁症（MDD）患者的背外侧前额叶皮质（dlPFC）中，神经元和神经胶质细胞的密度和体积减小。然而，这些细胞结构异常的基础以及它们之间的关系尚不清楚。我们假设，GABA 能神经元和神经胶质细胞密度的降低与 dlPFC 中谷氨酸能神经递质传递的改变有关。为了验证这一假设，我们检查了一种特定的标记物类型（即钙视网膜蛋白，CR：作为 GABA 能神经元的标志物），并试图确定与 dlPFC 中 CR 免疫反应性（IR）GABA 能神经元密度相关的神经病理学标志物，使用 Stanley 神经病理学联合会综合数据库（SNCID，http://sncid.stanleyresearch.org/），这是一个用于整合 Stanley 医学研究所（SMRI）数据集的基于网络的工具。我们发现，MDD 患者（n=15）dlPFC Ⅰ层 CR-IR GABA 能神经元的密度明显低于未受影响的对照组（n=15）（p=0.021）。CR-IR GABA 能神经元的变化与 SNC 所有受试者（n=60）dlPFC 中几种神经胶质细胞和锥体细胞标志物的变化呈正相关。我们还发现，谷氨酸变化与 SNC 所有受试者前额叶皮质中神经胶质纤维酸性蛋白（GFAP）表达水平和 CR-IR GABA 能神经元密度呈负相关（P<0.05）。这些发现为谷氨酸能神经递质传递增加导致 MDD 患者 dlPFC 中神经元和神经胶质细胞发生兴奋性毒性损伤的机制提供了一些见解。
