Chen Wen-Jin, Du Jian-Kui, Hu Xing, Yu Qing, Li Dong-Xia, Wang Chang-Nan, Zhu Xiao-Yan, Liu Yu-Jian
School of Kinesiology, The Key Laboratory of Exercise and Health Sciences of Ministry of Education, Shanghai University of Sport, Shanghai 200438, China; Department of Physiology, Second Military Medical University, Shanghai 200433, China.
Department of Physiology, Second Military Medical University, Shanghai 200433, China.
Physiol Behav. 2017 Dec 1;182:54-61. doi: 10.1016/j.physbeh.2017.09.024. Epub 2017 Sep 28.
Growing evidence suggests that inflammatory processes may be involved in depressive disorders. Inflammation is known to induce mitochondrial dysfunction in the nervous system. However, whether mitochondrial dysfunction is involved in the occurrence of inflammation-induced depressive-like behavior remains to be investigated. The present study aims to firstly, clarify whether mitochondrial dysfunction contributes to lipopolysaccharide (LPS)-induced depression-like behavior in mice and secondly, determine whether the anti-oxidant resveratrol alleviates inflammation-induced depressive-like behavior through the prevention of mitochondrial dysfunction in the hippocampus. We found that the administration of LPS led to mitochondrial oxidative stress and dysfunction as evidenced by increased mitochondrial superoxide production and decreased mitochondrial membrane potential and ATP production in the hippocampus. These effects were attenuated by intracerebroventricular (ICV) Injection of the mitochondria-targeted antioxidant Mito-TEMPO. LPS-treated mice displayed depressive-like behaviors as evidenced by reduced sucrose preference, increased immobility time and decreased struggling time in the forced swimming test. Both Mito-TEMPO and resveratrol could significantly improve the LPS-induced depressive-like behaviors. In contrast, ICV Injection of rotenone, the mitochondrial respiratory chain inhibitor, induced mitochondrial oxidative stress and dysfunction in the hippocampus, and resulted in depressive-like behaviors. Moreover, resveratrol alleviated the LPS-induced apoptosis of hippocampal cells. The antidepressant action of resveratrol was accomplished through the interruption of mitochondrial oxidative stress and the prevention of cell apoptosis in the hippocampus. These findings support the potential for resveratrol as a possible pharmacological agent for depression treatment in the future.
越来越多的证据表明，炎症过程可能与抑郁症有关。已知炎症会诱导神经系统中的线粒体功能障碍。然而，线粒体功能障碍是否参与炎症诱导的抑郁样行为的发生仍有待研究。本研究旨在首先阐明线粒体功能障碍是否导致小鼠脂多糖（LPS）诱导的抑郁样行为，其次确定抗氧化剂白藜芦醇是否通过预防海马体中的线粒体功能障碍来减轻炎症诱导的抑郁样行为。我们发现，LPS的给药导致线粒体氧化应激和功能障碍，海马体中线粒体超氧化物生成增加、线粒体膜电位降低和ATP生成减少证明了这一点。脑室内（ICV）注射线粒体靶向抗氧化剂Mito-TEMPO可减弱这些影响。LPS处理的小鼠表现出抑郁样行为，在强迫游泳试验中蔗糖偏好降低、不动时间增加和挣扎时间减少证明了这一点。Mito-TEMPO和白藜芦醇都可以显著改善LPS诱导的抑郁样行为。相比之下，脑室内注射线粒体呼吸链抑制剂鱼藤酮会诱导海马体中的线粒体氧化应激和功能障碍，并导致抑郁样行为。此外，白藜芦醇减轻了LPS诱导的海马体细胞凋亡。白藜芦醇的抗抑郁作用是通过中断线粒体氧化应激和预防海马体中的细胞凋亡来实现的。这些发现支持了白藜芦醇未来作为一种可能的抑郁症治疗药物的潜力。
