抑郁症与代谢综合征密切相关，因此被称为"II型代谢综合征"。过氧化物酶体增殖物激活受体 (peroxisome proliferation-activated receptors， PPARs)不仅在代谢综合征中发挥关键作用，而且具有神经保护作用。申请者的前期研究发现，PPARs激动药具有抗抑郁效应，提示PPARs在抑郁症病理过程中扮演着重要的角色。因此，本申请项目拟在前期研究的基础上，应用系统生物学研究方法从在体和离体水平、研究PPARs三种受体亚型（尤其是高表达于脑内的PPARβ/δ受体亚型）在抑郁症中的作用和机制，以及PPARs三种受体亚型抗抑郁作用的相互调控模式；研究PPARs对抑郁症中星形胶质细胞功能和神经再生障碍的调节作用及机制。预期研究结果将揭示PPARs抗抑郁的新的药理作用，为抑郁症病理机制的研究和基于PPARs的"非单胺类"抗抑郁新药的研发提供新靶标和实验依据。

The pathogenesis of depression is closely bound up with metabolic syndrome, so depression is also called "metabolic syndrome type II". Peroxisome proliferator-activated receptors (PPARs) not only play crucial roles in metabolic syndrome, but also play neuroprotective actions against neural injury. Our previous studies showed that PPAR agonists could play anti-depressive effects, indicating that PPARs might play important roles in depression. Therefore, the present project is to investigate the impacts of three subtypes of PPARs, including PPARα, PPARβ/δ(mostly expressed in brain) and PPARγ, in depression; to delineate how one subtype of PPARs interacts with other receptors and determine the functional significance of these interactions. Moreover, this project is to determine the functional roles of PPARs in astrocytes and hippocampal neurogenesis, and to disclose the involved molecular mechanisms in these functions. Our expected results would reveal the new pharmacological actions of anti-depression mediated by PPARs, and provide new targets for developing "non monoamine" anti-depressive drugs, and provide experimental evidences for exploring new pathological mechanisms of depression.