N-acetyl cysteine restores brain glutathione loss in combined 2-cyclohexene-1-one and D-amphetamine-treated rats: Relevance to schizophrenia and bipolar disorder
N-acetyl cysteine restores brain glutathione loss in combined 2-cyclohexene-1-one and D-amphetamine-treated rats: Relevance to schizophrenia and bipolar disorder
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DOI：
10.1016/j.neulet.2011.05.027
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发表时间：
2011-07-25
影响因子：
2.5
通讯作者：
Bush, Ashley I.
中科院分区：
文献类型：
--
作者：
Dean, Olivia M.;van den Buuse, Maarten;Bush, Ashley I.
氧化应激和大脑谷胱甘肽水平降低与精神分裂症和双相情感障碍有关。N-乙酰半胱氨酸(NAC)是谷胱甘肽的前体，对谷氨酸的神经传递、神经发生和炎症有额外的作用。虽然NAC治疗对精神分裂症和双相情感障碍都有好处，但其作用机制在很大程度上尚不清楚。同样，在精神疾病中，氧化应激和改变的多巴胺能活动之间的相互作用还没有特征。本研究观察了NAC对2-环己烯-1-酮(CHX，75 mg/kg)、D-苯丙胺(2.5 mg/kg)和/或2-环己烯-1-酮(CHX，75 mg/kg)所致大鼠脑谷胱甘肽耗竭的修复作用。ChX，而不是安非他明，导致纹状体和额叶皮质谷胱甘肽水平显著下降。NAC(1000 mg/kg)可逆转生理盐水组和苯丙胺组(仅额叶皮质)大鼠的谷胱甘肽耗竭。虽然NAC在这个模型中被证明是有益的，但苯丙胺和CHX联合使用时缺乏额外的谷胱甘肽耗竭，并不支持氧化应激和改变的多巴胺传递之间的终结性相互作用。(C)2011爱思唯尔爱尔兰有限公司。保留所有权利。
Oxidative stress and reduced brain levels of glutathione have been implicated in schizophrenia and bipolar disorder. N-acetyl cysteine (NAC) is a precursor of glutathione and has additional effects on glutamate neurotransmission, neurogenesis and inflammation. While NAC treatment has shown benefits in both schizophrenia and bipolar disorder, the mechanisms of action are largely unknown. Similarly, the interaction between oxidative stress and altered dopaminergic activities in psychiatric illness is not yet characterized. This study investigated the capacity of NAC in restoring brain glutathione depletion in rats that received 2-cyclohexene-1-one (CHX, 75 mg/kg), D-amphetamine (2.5 mg/kg) or both. CHX, but not amphetamine, induced significant depletion of glutathione levels in the striatum and frontal cortex. Glutathione depletion was reversed by NAC (1000 mg/kg) in saline-treated and amphetamine-treated (frontal cortex only) rats. While NAC was shown to be beneficial in this model, the lack of additional glutathione depletion by amphetamine in combination with CHX does not support a summative interaction between oxidative stress and altered dopamine transmission. (C) 2011 Elsevier Ireland Ltd. All rights reserved.