帕金森病（PD）的病因和机制目前尚未完全阐明，多巴胺能（DA）神经元退变引起的DA递质减少是PD运动障碍症状的主要病理基础。近年来研究发现PD患者脑内存在乳酸含量增高的现象，且酸敏感离子通道（ASICs）抑制剂对PD小鼠具有一定的保护作用，提示ASICs的异常激活可能参与PD发病机制，但其具体机制未明。我们最近的研究发现，MPP+能诱导ASICs异常激活，促进DA递质释放。本研究将在此基础上，运用分子生物学及电生理等技术，结合药理学方法深入研究ASIC1a对黑质纹状体通路DA递质释放的影响；同时采用ASIC1基因敲除小鼠在体验证ASIC1a在PD发病中的作用及机制。本研究有望揭示ASIC1a在PD致病机制中的具体作用，从而为临床治疗PD提供新的思路和靶标。

Parkinson s disease (PD) is a common neurodegenerative disorder, and characterized by progressive losses of dopaminergic neurons in substantia nigra associated with dopamine depletion in striatum. Recent studies showed the enhanced lactate levels in the brains of PD patients. Acid sensing ion channels (ASICs) blockers, amiloride and PcTx1, exerted neuroprotective effects in a mouse model of PD, implying a role of ASICs in the pathogenesis of PD. However, the role and underlying mechanisms of ASICs in PD have not been fully elucidated. Our preliminary data demonstrated that MPP+ caused abnormal activation of ASIC1a and induced the increase of dopamine release. This process could be attenuated by ASIC1a specific blocker. Howerver, the physiological function of ASIC1a in dopamine release is still unknown. This project is designed to explore the roles of ASIC1a in dopamine release; to assess whether ASIC1a is involved in PD development by using ASIC1 knock out mouse. The findings of this work will make contributions to clarify the possible pathogenic factor of PD and also provide novel theoretical and experimental evidence in searching for promising therapeutic target of PD.