Decreased levels of glutathione, the major brain antioxidant, in post-mortem prefrontal cortex from patients with psychiatric disorders
Decreased levels of glutathione, the major brain antioxidant, in post-mortem prefrontal cortex from patients with psychiatric disorders
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DOI：
10.1017/s1461145710000805
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发表时间：
2011-02-01
影响因子：
4.8
通讯作者：
Young, L. Trevor
中科院分区：
文献类型：
--
作者：
Gawryluk, Jeremy W.;Wang, Jun-Feng;Young, L. Trevor
积累的数据表明，氧化应激可能是双相情感障碍（BD），重性抑郁症（MDD）和精神分裂症（SCZ）的病理生理学基础的一个因素。谷胱甘肽（GSH）是脑内主要的自由基清除剂。GSH水平降低会增加细胞对氧化应激的脆弱性;其特征是积累活性氧。本研究的目的是确定情绪障碍和SCZ是否与异常GSH及其功能相关酶相关。来自BD、MDD、SCZ患者和来自非精神病对照组的尸检前额叶皮层由Stanley Foundation Neuropathology Consortium提供。分光光度法用于GSH的定量测定，而免疫印迹分析用于检查谷氨酰-半胱氨酸连接酶（GCL），GSH还原酶（GR）和GSH过氧化物酶（GPx）的表达。我们发现，与对照组相比，所有精神病患者的还原型、氧化型和总GSH水平均显著降低。尽管各组之间的GCL和GR水平没有差异，但与对照组相比，MDD和SCZ中的GPx水平降低。由于氧化损伤已被证明在MDD，BD和SCZ，我们的发现，GSH水平降低，在死后的前额叶皮质表明，这些患者群体可能更容易受到氧化应激。
Accruing data suggest that oxidative stress may be a factor underlying the pathophysiology of bipolar disorder (BD), major depressive disorder (MDD), and schizophrenia (SCZ). Glutathione (GSH) is the major free radical scavenger in the brain. Diminished GSH levels elevate cellular vulnerability towards oxidative stress; characterized by accumulating reactive oxygen species. The aim of this study was to determine if mood disorders and SCZ are associated with abnormal GSH and its functionally related enzymes. Post-mortem prefrontal cortex from patients with BD, MDD, SCZ, and from non-psychiatric comparison controls were provided by the Stanley Foundation Neuropathology Consortium. Spectrophotometric analysis was utilized for the quantitative determination of GSH, while immunoblotting analyses were used to examine expression of glutamyl-cysteine ligase (GCL), GSH reductase (GR), and GSH peroxidase (GPx). We found that the levels of reduced, oxidized, and total GSH were significantly decreased in all psychiatric conditions compared to the control group. Although GCL and GR levels did not differ between groups, the levels of GPx were reduced in MDD and SCZ compared to control subjects. Since oxidative damage has been demonstrated in MDD, BD, and SCZ, our finding that GSH levels are reduced in post-mortem prefrontal cortex suggests that these patient groups may be more susceptible to oxidative stress.