PNAS：脂联素帮助缓解小鼠的抑郁症

近日，科研人员在国际杂志PNAS上报告说，血液循环中的一种代谢激素帮助缓解小鼠的抑郁症症状。此前的研究已经表明了II型糖尿病患者患抑郁症的风险增加。Xin-Yun Lu及其同事检验了一种来自脂肪细胞的激素脂联素 (Adiponectin) ——已知它能控制糖和脂肪的代谢，并且已知它能穿过血脑屏障——是否在抑郁症中起到了作用。这组作者让小鼠在一个既有的实验范式中接受14天的重复的社会压力，在这种环境中，小鼠在遭遇不熟悉、侵略性的对手的时候被击败了。

在最后一次遭遇的一或两天之后测量了被击败的小鼠的血浆中的脂联素水平。这组作者发现，社会受挫恰逢总的血浆脂联素水平下降。此外，与正常小鼠相比，因为遗传而缺乏脂联素的小鼠表现出增加了的抑郁相关症状的易感性，这包括社会厌恶，追求奖赏的表现降低，以及习得的无助——在这种情况中，这些小鼠拒绝了改善它们的境况的机会。

然而，这组作者报告说，向小鼠大脑注射重组脂联素在正常小鼠和糖尿病小鼠身上引发了抗抑郁药物样的效应。这组作者说，脂联素可能成为治疗人们的抑郁症的一种潜在的治疗靶标，特别是对于那些患有糖尿病的抑郁症病人。

doi:10.1073/pnas.1202835109
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Adiponectin is critical in determining susceptibility to depressive behaviors and has antidepressant-like activity

Jing Liua, Ming Guoa, Di Zhanga, Shao-Ying Chenga, Meilian Liua, Jun Dinga, Philipp E. Schererb, Feng Liua, and Xin-Yun Lua,c,1,2

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.