NLRP3 inflammasome activation by mitochondrial reactive oxygen species plays a key role in long-term cognitive impairment induced by paraquat exposure
NLRP3 inflammasome activation by mitochondrial reactive oxygen species plays a key role in long-term cognitive impairment induced by paraquat exposure
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DOI：
10.1016/j.neurobiolaging.2015.05.018
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发表时间：
2015-09-01
影响因子：
4.2
通讯作者：
Ran, Qitao
中科院分区：
文献类型：
--
作者：
Chen, Liuji;Na, Ren;Ran, Qitao
暴露于农药等环境毒素会增加阿尔茨海默病的风险。在这项研究中，我们研究了百草枯暴露对阿尔茨海默病动物模型APP/PS1小鼠和野生型（WT）小鼠认知的长期影响。我们的研究结果表明，APP/PS1小鼠在百草枯暴露后5个月认知功能障碍加重，A β水平升高，WT小鼠在百草枯暴露后5个月和16个月认知功能障碍。此外，在接触百草枯的APP/PS1小鼠和WT小鼠中均观察到线粒体氧化应激增加和脑部炎症加剧。有趣的是，NLRP 3炎性体的激活在百草枯暴露的小鼠中得到增强，该炎性体在响应线粒体应激时触发炎症。此外，过表达Prdx 3（一种解毒线粒体H2 O2的关键酶）的转基因小鼠抑制了NLRP 3炎性体激活，减少了大脑炎症，并减轻了百草枯暴露后的认知障碍。总之，我们的研究结果表明，由线粒体活性氧诱导的NLRP 3炎性体激活通过升高脑炎症在介导百草枯诱导的长期认知能力下降中起着关键作用。爱思唯尔公司出版
Exposure to environmental toxins such as pesticides is implicated in increasing Alzheimer's disease risk. In this study, we investigated the long-term effects of paraquat exposure on cognition of Alzheimer's disease animal model APP/PS1 mice and wild-type (WT) mice. Our results showed that APP/PS1 mice had exacerbated cognition impairment and elevated A beta levels at 5 months after paraquat exposure, and that WT mice had cognition impairment at 5 and 16 months after paraquat exposure. In addition, increased mitochondrial oxidative stress and augmented brain inflammation were observed in both paraquat-exposed APP/PS1 mice and WT mice. Interestingly, activation of NLRP3 inflammasome, which triggers inflammation in response to mitochondrial stress, was enhanced in paraquat-exposed mice. Moreover, transgenic mice overexpressing Prdx3, a key enzyme in detoxifying mitochondrial H2O2, had suppressed NLRP3 inflammasome activation, reduced brain inflammation, and attenuated cognition impairment after paraquat exposure. Together, our results indicate that NLRP3 inflammasome activation induced by mitochondrial reactive oxygen species plays a key role in mediating paraquat-induced long-term cognition decline by elevating brain inflammation. Published by Elsevier Inc.