骨与中枢存在密切的相互调节。成骨细胞来源的骨钙素(OCN)不仅可调控血糖稳态、全身能量代谢与男性生殖功能，还可调控认知功能与大脑发育。帕金森病(PD)是最常见的神经退行性运动障碍疾病，典型病理特征是多巴胺能神经元内α-synuclein沉积形成路易小体。有研究认为该病变起源于肠道，且肠道菌群紊乱在PD运动障碍和神经炎性反应发生中发挥重要作用。因此改善肠道菌群紊乱可成为防治PD发生发展的一个重要手段。本课题组在前期工作中发现，OCN不仅可促进多巴胺能神经元恢复、改善PD大鼠运动功能，还可影响其肠道菌群分布，因此探索OCN对肠道菌群的调节可为PD防治提供新的思路。本研究将利用α-synuclein过表达PD模型小鼠、GPR158 knock-down AAV等，探究OCN通过改善肠道菌群紊乱调控PD黑质纹状体功能的机制。本研究将扩大骨作为内分泌器官的内涵，为帕金森病发病机制提供新观点。

A close correlation was found between bone homeostasis and central nervous system (CNS). Osteoblast-derived osteocalcin (OCN) was found to has diverse effects on whole body metabolism, not only involved in energy metabolism and male fertility, but also in the regulation of CNS. Parkinson’s disease is the most common neurodegenerative movement disorder, with the typical pathology of accumulation of α-synuclein in dopaminergic neurons, which we called Lewy body. Some studies believed this pathology originated from gut and gut microbiota dysbiosis was found to contribute to the motor deficits and neuroinflammation in PD. Therefore, improving the microbiota homeostasis can become an effective method to prevent PD development. Our previous works demonstrated that administration of OCN brought significant benefits on motor deficits, dopaminegic neurons and microbiota dysbioss of 6-OHDA induced PD rats. Thus, exploration of OCN’s function on gut microbiota can provide a new treatment for PD. With the use of α-synuclein-overexpression PD mice and GPR158 knock-down AAV, we aim to explore the mechanisms of OCN in regulating gut microbiota to improve nigrostriatal funtion of PD. This study may help to expand the scope of skeleton physiology as an endocrine organ and provide a new elaboraton for the pathogenesis of PD.