Mitochondrial function in the brain links anxiety with social subordination
Mitochondrial function in the brain links anxiety with social subordination
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DOI：
10.1073/pnas.1512653112
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发表时间：
2015-12-15
影响因子：
11.1
通讯作者：
Sandi, Carmen
中科院分区：
文献类型：
--
作者：
Hollis, Fiona;van der Kooij, Michael A.;Sandi, Carmen
支配等级是社会群体不可或缺的一部分，但人格特质是否会使个体倾向于某一特定等级仍不清楚。在这里，我们表明，特质焦虑直接影响雄性远交大鼠的社会优势，并确定了一个重要的介导作用，线粒体功能的神经核。在与低焦虑大鼠的社交接触中，高焦虑动物倾向于成为从属动物，表现出线粒体复合物I和II蛋白质和呼吸能力降低，以及ATP减少和髓核中ROS产生增加。药理学方法表明这些结果存在因果关系。在焦虑匹配的动物之间的二元竞争中，将特定的线粒体复合物I或II抑制剂微输注到核内，降低了社会等级，模仿了在高度焦虑的动物中观察到的低概率成为主导。相反，脑内注射烟酰胺（一种已知能增强大脑能量代谢的维生素B3酰胺形式），可防止高度焦虑个体出现从属状态。我们的结论是，线粒体功能的神经核是至关重要的社会等级制度的建立，并在低社会竞争力与高度焦虑的关键参与。我们的研究结果强调了大脑能量代谢在社会行为中的关键作用，并指出了线粒体功能在神经核中作为一个潜在的标志物和治疗焦虑相关的社会障碍的途径。
Dominance hierarchies are integral aspects of social groups, yet whether personality traits may predispose individuals to a particular rank remains unclear. Here we show that trait anxiety directly influences social dominance in male outbred rats and identify an important mediating role for mitochondrial function in the nucleus accumbens. High-anxious animals that are prone to become subordinate during a social encounter with a low-anxious rat exhibit reduced mitochondrial complex I and II proteins and respiratory capacity as well as decreased ATP and increased ROS production in the nucleus accumbens. A causal link for these findings is indicated by pharmacological approaches. In a dyadic contest between anxiety-matched animals, microinfusion of specific mitochondrial complex I or II inhibitors into the nucleus accumbens reduced social rank, mimicking the low probability to become dominant observed in high-anxious animals. Conversely, intraaccumbal infusion of nicotinamide, an amide form of vitamin B3 known to enhance brain energy metabolism, prevented the development of a subordinate status in high-anxious individuals. We conclude that mitochondrial function in the nucleus accumbens is crucial for social hierarchy establishment and is critically involved in the low social competitiveness associated with high anxiety. Our findings highlight a key role for brain energy metabolism in social behavior and point to mitochondrial function in the nucleus accumbens as a potential marker and avenue of treatment for anxiety-related social disorders.