Effect of chronic corticosterone-induced depression on circadian rhythms and age-related phenotypes in mice
Effect of chronic corticosterone-induced depression on circadian rhythms and age-related phenotypes in mice
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慢性皮质酮诱导的抑郁症对小鼠昼夜节律和年龄相关表型的影响
DOI：
10.1093/abbs/gmy132
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发表时间：
2018-12-01
影响因子：
3.7
通讯作者：
Fu, Zhengwei
中科院分区：
文献类型：
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作者：
Ma, Lingyan;Shen, Qichen;Fu, Zhengwei
昼夜节律紊乱是抑郁症的一种公认的影响，我们之前的文章证明了抑郁症和过早衰老之间的联系，但其潜在机制还不清楚。在本研究中，我们使用慢性皮质酮（CORT）治疗抑郁症的小鼠模型，以阐明抑郁症可能与昼夜节律钟和介导年龄相关表型的机制。小鼠每天注射CORT 20 mg/kg，连续21 d，通过蔗糖摄入试验、悬尾试验和旷场试验观察小鼠抑郁样行为。我们的研究结果表明，CORT注射可能与生物钟通过损害昼夜节律或改变时钟基因的相位值。我们还发现，CORT治疗的小鼠表现出显着的逐渐减少体重增加的氧化应激，包括抗氧化剂相关酶的活性降低，还原型谷胱甘肽：谷胱甘肽二硫化物的比例和细胞色素（Cyt）-C水平，和活性氧含量升高。此外，慢性CORT注射影响炎症反应，线粒体ATP的产生和端粒缩短，这可能与Sirtuin 3（SIRT 3）信号通路有关。此外，慢性CORT注射打乱了衰老表型的一些指标的昼夜节律，并改变了这些指标的相位值。我们的研究结果表明，心理压力条件，如抑郁症与昼夜节律和年龄相关表型的变化有关。
Disrupted circadian rhythms are a recognized effect of depression, and our previous article demonstrated an association between depression and premature aging, but the underlying mechanisms are not well understood. In the present study, we used a mouse model of chronic corticosterone (CORT)-treated depression to elucidate a mechanism by which depression may be associated with the circadian clock and mediate age-related phenotypes. Mice received a daily injection of 20 mg/kg CORT for 21 consecutive days, and the depression-like behaviors of mice were identified by the sucrose intake test, tail suspension test and open field test. Our findings indicated that CORT injection may be correlated with the circadian clock by impairing circadian rhythms or shifting the phase values of clock genes. We also showed that CORT-treated mice exhibited a significant gradual reduction in body weight gain with increased oxidative stress, including reduced activity of antioxidant-related enzymes, reduced glutathione:glutathione disulfide ratio and cytochrome (Cyt)-C level, and elevated reactive oxygen species content. Moreover, chronic CORT injection affected inflammatory responses, the production of mitochondrial ATP and telomere shortening, which may be associated with the Sirtuin 3 (SIRT3) signaling pathway. Additionally, chronic CORT injection disrupted the circadian rhythms of some indexes of aging phenotypes and altered the phase values of these indexes. Our findings suggest that psychologically stressful conditions such as depression are linked to changes in circadian rhythms and age-related phenotypes.