Adiponectin is critical in determining susceptibility to depressive behaviors and has antidepressant-like activity
Adiponectin is critical in determining susceptibility to depressive behaviors and has antidepressant-like activity
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DOI：
10.1073/pnas.1202835109
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发表时间：
2012-07-24
影响因子：
11.1
通讯作者：
Lu, Xin-Yun
中科院分区：
文献类型：
--
作者：
Liu, Jing;Guo, Ming;Lu, Xin-Yun
抑郁症是一种使人衰弱的精神疾病，通常与代谢紊乱如2型糖尿病共病。脂联素是一种脂肪细胞源性激素，具有抗糖尿病和胰岛素增敏作用。在这里，我们表明，血浆中的脂联素水平降低，在慢性社会失败的压力抑郁症模型，这与减少社会交往时间。由单倍性不足引起的脂联素水平降低导致对社交厌恶、“快感缺失”和习得性无助的易感性增加，并导致糖皮质激素介导的下丘脑-垂体-肾上腺（HPA）轴负反馈受损。脑室内（i. c. v.）注射脂联素中和抗体可加速应激诱导的抑郁样行为。相反，i. c. v.给予外源性脂联素在正常体重小鼠和饮食诱导的肥胖糖尿病小鼠中产生抗抑郁样行为效应。综上所述，这些结果表明脂联素在抑郁样行为中的关键作用，并指出了抑郁症的潜在创新治疗方法。
Depression is a debilitating mental illness and is often comorbid with metabolic disorders such as type 2 diabetes. Adiponectin is an adipocyte-derived hormone with antidiabetic and insulin-sensitizing properties. Here we show that adiponectin levels in plasma are reduced in a chronic social-defeat stress model of depression, which correlates with decreased social interaction time. A reduction in adiponectin levels caused by haploinsufficiency results in increased susceptibility to social aversion, "anhedonia," and learned helplessness and causes impaired glucocorticoid-mediated negative feedback on the hypothalamic-pituitary-adrenal (HPA) axis. Intracerebroventricular (i.c.v.) injection of an adiponectin neutralizing antibody precipitates stress-induced depressive-like behavior. Conversely, i.c.v. administration of exogenous adiponectin produces antidepressant-like behavioral effects in normal-weight mice and in diet-induced obese diabetic mice. Taken together, these results suggest a critical role of adiponectin in depressive-like behaviors and point to a potential innovative therapeutic approach for depressive disorders.