實(shí)驗(yàn)室在《Molecular Psychiatry》發(fā)表題為“Role of the adipose PPARγ-adiponectin axis in susceptibility to stress and depression/anxiety-related behaviors”的文章.
課題組于12月13日在《Molecular Psychiatry》 （精神病學(xué)1區(qū)期刊，IF：13.3）上在線發(fā)表研究論文 “Role of the adipose PPARγ-adiponectin axis in susceptibility to stress and depression/anxiety-related behaviors”。
抑郁和焦慮是目前社會中最常見的心理疾病，嚴(yán)重影響人們的生活和工作，近年來患病率病逐年漸增加，給社會和經(jīng)濟(jì)帶來沉重負(fù)擔(dān)。本課題組在國際上首先提出精神疾病的“代謝假說”，發(fā)現(xiàn)了內(nèi)分泌系統(tǒng)中的脂肪組織與情緒調(diào)節(jié)相關(guān)的神經(jīng)系統(tǒng)之間的相互作用。本研究在 “代謝假說”基礎(chǔ)上，進(jìn)一步探討了脂肪組織在應(yīng)激誘導(dǎo)的抑郁行為中的作用。應(yīng)用慢性社會挫?。╟hronic social defeat）應(yīng)激模型發(fā)現(xiàn)小鼠對應(yīng)激誘導(dǎo)的社會逃避抑郁行為的易感性與脂肪中脂聯(lián)素上游調(diào)控基因PPARγ2水平之間存在顯著相關(guān)性。利用PPARγ激動劑rosiglitazone激活PPARγ信號通路具有抗抑郁和抗焦慮作用，并伴有脂肪和血液中脂聯(lián)素水平的升高。Rosiglitazone的作用可以被脂聯(lián)素的缺失或PPARγ拮抗劑GW9662所阻斷。本研究在國際上首次證明脂肪組織PPARγ-脂聯(lián)素信號系統(tǒng)在應(yīng)激易感性中的作用和對抑郁、焦慮行為的調(diào)控，并為開發(fā)新型抗抑郁和焦慮藥物提供了新的靶點(diǎn)。
Mol Psychiatry. 2016 Dec 13. doi: 10.1038/mp.2016.225. [Epub ahead of print]
Role of the adipose PPARγ-adiponectin axis in susceptibility to stress and depression/anxiety-related behaviors.
Guo M1, Li C1, Lei Y2, Xu S1, Zhao D1, Lu XY1,2,3.
Author information
1Institute for Metabolic and Neuropsychiatric Disorders, Binzhou Medical University Hospital, Binzhou, China.
2Department of Pharmacology, The University of Texas Health Science Center at San Antonio, San Antonio, TX, USA.
3Department of Psychiatry, The University of Texas Health Science Center at San Antonio, San Antonio, TX, USA.
Abstract
Adaptive responses to stressful stimuli involving behavioral, emotional and metabolic changes are orchestrated by the nervous and endocrine systems. Adipose tissue has been recognized as a highly active metabolic and endocrine organ, secreting adipokines that operate as hormones to mediate the crosstalk with other organs including the brain. The role of adipose tissue in sensing and responding to emotional stress and in behavioral regulation, however, remains largely unknown. The nuclear receptor peroxisome proliferator-activated receptor gamma (PPARγ) is a key transcriptional factor controlling adipokine gene expression. Here we show that chronic social defeat stress decreases messenger RNA and protein levels of PPARγ in adipose tissue of susceptible but not resilient mice, which was correlated with social avoidance behavior. A corresponding reduction in adipose adiponectin production was observed in susceptible mice. Rosiglitazone, a blood-brain barrier-impermeant PPARγ-selective agonist, elicited antidepressant- and anxiolytic-like behavioral effects in wild-type mice, with a concurrent increase in plasma adiponectin levels. These effects of rosiglitazone were absent in mice lacking adiponectin but having normal PPARγ expression in adipose tissue and brain. Moreover, pretreatment with the PPARγ-selective antagonist GW9662 blocked rosiglitazone-induced adiponectin expression and antidepressant/anxiolytic-like effects. Together, these results suggest that the behavioral responses to rosiglitazone are mediated through PPARγ-dependent induction of adiponectin. Our findings support an important role for the adipose PPARγ-adiponectin axis in susceptibility to stress and negative emotion-related behaviors. Selectively targeting PPARγ in adipose tissue may offer novel strategies for combating depression and anxiety.Molecular Psychiatry advance online publication, 13 December 2016; doi:10.1038/mp.2016.225
文章鏈接：http://www.nature.com/mp/journal/vaop/ncurrent/abs/mp2016225a.html
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