Uncoupling protein 2 knockout exacerbates depression-like behaviors in mice via enhancing inflammatory response
Uncoupling protein 2 knockout exacerbates depression-like behaviors in mice via enhancing inflammatory response
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DOI：
10.1016/j.neuroscience.2011.05.047
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发表时间：
2011-09
期刊：
影响因子：
3.3
通讯作者：
X.-L. Sun;Y. Liu;T. Dai;Jian-hua Ding;G. Hu
中科院分区：
文献类型：
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作者：
X.-L. Sun;Y. Liu;T. Dai;Jian-hua Ding;G. Hu
线粒体解偶联蛋白2(UCP2)被认为是调节活性氧(ROS)产生的重要蛋白质。UCP2的缺失有可能促进ROS的积累，从而诱导氧化损伤和炎症反应。越来越多的证据有力地揭示了抑郁症伴随着氧化应激，因此本研究旨在探讨UCP2在抑郁症病因中的作用。采用野生型和UCP2基因敲除小鼠建立慢性轻度应激(CMS)诱导的抑郁症快感缺失模型。结果表明，CMS导致UCP2基因敲除小鼠出现更严重的抑郁反应，表现为抑郁样行为加剧，皮质酮水平升高，体重显著下降。此外，CMS导致UCP2基因敲除小鼠的死亡率更高。我们进一步的研究表明，UCP2基因敲除增强了CMS诱导的下丘脑核因子κB(NF-κB)p65的激活，并增加了肿瘤坏死因子-α的基因表达。即使在基础状态下，CMS也能显著提高UCP2基因敲除小鼠血清和脾组织中肿瘤坏死因子-α的水平。因此，我们的研究结果表明，UCP2基因敲除诱导的炎症可能有助于抑郁症状的发展。
Mitochondrial uncoupling protein 2 (UCP2) has been recognized as an important protein to regulate reactive oxygen species (ROS) production. The absence of UCP2 has the potential to promote ROS accumulation and thereby induces oxidative damages and inflammatory response. Increasing evidence strongly reveals that depression is accompanied by oxidative stress, so the present study was to investigate the impacts of UCP2 on the etiology of depression. Wild-type and UCP2 knockout mice were used to establish chronic mild stress (CMS)-induced anhedonia model of depression. The results showed that CMS led to more severe depressive responses in UCP2 knockout mice, characterized by exacerbated depression-like behaviors, increased corticosterone level and significant loss of weight. Moreover, CMS resulted in a higher mortality in UCP2 knockout mice. Our further study showed that UCP2 knockout enhanced CMS-induced activation of nuclear factor κB (NF-κB) p65 and increased mRNA expression of tumor necrosis factor alpha (TNF-α) in hypothalamus. And the levels of TNF-α of serum and spleen in UCP2 knockout mice are remarkably enhanced by CMS, even under basal conditions. Therefore, our findings suggest that UCP2 knockout-induced inflammation may contribute to the development of depressive symptoms.