小胶质细胞褪黑素1型受体（MT1）对神经炎症的调控及其在帕金森病发病中的作用

神经炎症在帕金森病（PD）的发生中有重要作用，小胶质细胞是神经炎症的主要介导者，因此，调控小胶质细胞的激活可能为临床帕金森病的治疗提供潜在靶点。随着机体的衰老，脑内会出现以小胶质细胞激活为特征的炎症的加剧。同时，在衰老过程中，机体的重要激素褪黑素及其1型受体（MT1）的表达都出现显著性减少。不仅如此，有研究表明，在PD患者中脑黑质，MT1的表达明显下调。那么生理性衰老过程中所引发的MT1的减少是否是导致衰老向PD发展的促进因素，该作用是否由神经炎症的加剧所介导的，亟待我们深入研究。因此，本项目将从动物、细胞和分子水平研究小胶质细胞上MT1受体对神经炎症的调控作用。利用小胶质细胞条件性敲除MT1受体的小鼠来研究其对神经炎症的作用,从而阐明生理性衰老向PD发展的推动因素。研究成果将有助于明确MT1途径对PD神经炎症的作用，揭示MT1受体功能障碍在衰老向PD发展中的作用，阐明PD发病新机制。

Neuroinflammation plays an important role in the development of Parkinson's disease (PD). Microglia are the main mediators of neuroinflammation. Therefore, regulation of microglia activation may provide a potential target for the treatment of Parkinson's disease. As the progress of aging. there is an increase in inflammation in the brain characterized by activation of microglia. At the same time, during the aging process, the body's important hormone melatonin and its receptor MT1 expression decreased significantly. Not only that, studies have shown that in the substantia nigra of PD patients, the expression of melatonin receptor MT1 is significantly down-regulated. Whether the reduction of melatonin receptor MT1 triggered by physiological aging is the driving factor for the development of aging to PD, and whether it is mediated by the increase of neuroinflammation is urgently needed. Therefore, this project will study the regulation of neuroinflammation by MT1 receptor on microglia at the animal, cellular and molecular levels. Microglial MT1 conditional knockout mouse will be used to elucidate its effects on neuroinflammation to clarify the driving factors for the development of physiological aging to PD. This research will help to clarify the role of MT1 pathway in neuroinflammation, reveal the role of MT1 receptor dysfunction in the development of aging to PD, and elucidate the new mechanism of PD pathogenesis.