过氧化物酶体增殖物活化受体（PPAR）是一组具有具有调控细胞发育与新陈代谢等功能的核受体蛋白，含3种亚型；其中PPARα在海马区有高量表达，能够与环磷酸腺苷反应元件结合蛋白（CREB）直接结合并促进其功能发挥及其下游产物表达。已知抑郁症，一种神经精神疾病，其病理机制与海马CREB高度相关，一切能够增强海马CREB功能的药物或手段都具有潜在的抗抑郁作用，因此我们推测PPARα可能是一个潜在的抑郁症靶点并参与抑郁症的病理生理过程；且目前尚无任何研究抑郁症与海马PPARα的关系的报道。我们的前期实验结果也表明抑郁症的确降低海马PPARα表达，并且激动PPARα蛋白能够显示抗抑郁作用，而抑制PPARα则显示促抑郁样效应。在此基础上，本课题将综合运用western blot、免疫共沉淀、组织免疫荧光、高尔基银染、腺病毒基因干预和各种抑郁行为学模型等技术，研究海马PPARα与抑郁症病理机制之间的关系。

Peroxisome proliferator-activated receptors (PPARs) are a group of transcription factors that are involved in cell development and metabolism. PPARs has three subtypes, in which PPARα is widely expressed in hippocampus, and able to enhance the physiological function of cAMP response element binding protein (CREB) by combining it directly. It is known that the pathophysiology of depression, a kind of neuropsychiatric disease, is closely correlated with hippocampal CREB. It is also supposed that all the compounds/means that could enhance hippocampal CREB function have potential antidepressant effects, so we assumed that PPARα may be involved in the pathophysiology of depression and also a potential target for antidepressants. By now, there are no reports on the role of hippocampal PPARα in the pathophysiology of depression. Besides, our preliminary data showed that the hippocampal PPARα expression of depression model mice is indeed decreased compared to wild-type mice, and activation of hippocampal PPARα could produce antidepressant effects, while inhibition of hippocampal PPARα showed pro-depressant effects. Based on these evidences, we are going to use various methods, including western blot, co-immunoprecipitation, immunofluorescence, golgi-staining, lentiviral-gene interference and different depression models, to explore the role of PPARα in the pathophysiology of depression.