Cholecystokinin-8 inhibits methamphetamine-induced neurotoxicity via an anti-oxidative stress pathway
Cholecystokinin-8 inhibits methamphetamine-induced neurotoxicity via an anti-oxidative stress pathway
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Cholecystokinin-8 通过抗氧化应激途径抑制甲基苯丙胺诱导的神经毒性
DOI：
10.1016/j.neuro.2016.08.008
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发表时间：
2016-12-01
期刊：
影响因子：
3.4
通讯作者：
Cong, Bin
中科院分区：
文献类型：
--
作者：
Wen, Di;An, Meiling;Cong, Bin
甲基苯丙胺作为一种强有力的成瘾精神刺激剂，再加上其神经毒性，滥用甲基苯丙胺可能会导致大脑结构和功能的长期异常。我们发现，CCK-8可抑制冰毒所致的纹状体和黑质多巴胺能神经元的损伤，以及相关的行为缺陷和体温升高。然而，CCK-8对冰毒的作用机制尚不清楚。本研究旨在探讨CCK-8对冰毒所致神经毒性的可能保护作用是否涉及抗氧化应激机制。并研究了CCK受体亚型对CCK-8的调节作用。结果表明，CCK-8通过激活CCK2受体亚型，剂量依赖性地抑制METH诱导的细胞毒作用。在冰毒刺激前预先处理CCK-8可显著降低PC12细胞内活性氧的产生和NADPH氧化酶的活性。总之，我们的研究证实了CCK-8在体外对冰毒诱导的神经毒性的保护作用，并提示该作用的一个可能机制是通过激活CCK2受体来减轻冰毒刺激引起的神经毒性和氧化应激。(C)2016爱思唯尔B.V.保留所有权利。
As a powerful addictive psychostimulant drug, coupled with its neurotoxicity, methamphetamine (METH) abuse may lead to long-lasting abnormalities in brain structure and function. We found that pretreatment of cholecystokinin-8 (CCK-8) inhibited METH-induced brain cellular dopaminergic (DA) damage in the striatum and substantia nigra, and related behavioural deficits and hyperthermia. However, the mechanism of CCK-8 action on METH-induced toxicity is not clear. The aim of this study was to explore whether the possible protective effect of CCK-8 on METH-induced neurotoxicity involved anti-oxidative stress mechanisms. The subtypes of CCK receptors mediating the regulatory action of CCK-8 were also investigated. The present results revealed that CCK-8 dose-dependently inhibited METH induced cytotoxic effect by activating the CCK2 receptor subtype in PC12 cells and CCK2 receptor stable transfected-HEK293 cells. Pre-treatment of CCK-8 before METH stimulation significantly attenuated the generation of reactive oxygen species and NADPH oxidase activation in PC12 cells. In conclusion, our study demonstrated a protective effect of CCK-8 on METH-induced neurotoxicity in vitro and suggested that a possible mechanism of this action was dependent on the activation of the CCK2 receptor to reduce the neurotoxicity and oxidative stress induced by METH stimulation. (C) 2016 Elsevier B.V. All rights reserved.