帕金森病（PD）是常见的神经变性疾病，但其病因和发病机制仍未明确。自噬异常和星形胶质细胞功能改变在PD发生中都扮演了重要角色。最近有文献报道激活星形胶质细胞多巴胺D2受体（DRD2）能抑制脑内炎症，DRD2表达下调或缺失加重神经炎症反应。我们最近发现DRD2受体激动剂能上调星形胶质细胞自噬，且自噬底物蛋白P62敲减能抑制炎症反应；然而，星形胶质细胞自噬是否介导DRD2对炎症反应的调控、并且星形胶质细胞自噬是否及如何参与PD发病都未明，亟待深入研究。因此，本项目将从动物、细胞和分子水平，研究DRD2对星形胶质细胞自噬的调控，分别运用星形胶质细胞Atg7条件性敲除小鼠和Atg7过表达研究星形胶质细胞自噬在DRD2抑制神经炎症反应中的作用和分子机制。研究成果将有助于明确DRD2途径对细胞自噬的作用，揭示星形胶质细胞自噬对神经炎症等PD病理过程的调控，阐明PD发病新机制。

Parkinson disease (PD) is a common neurodegenerative disease, but its etiology and pathogenesis are still not clear. Astrocyte activation and its functional changes play an important role in the development of PD, such as chronic neuroinflammation,, reduced secretion of neurotrophic factors, and transmission of prion-like pathological changes. Activation of astrocytic dopamine receptor subtype 2 (DRD2) plays a role in inhibiting inflammation in the brain, and DRD2 deficiency or down-regulation accelerates the neuroinflammatory responses; however, whether this is associated with autophagic activity changes in astrocytes is not clear yet. Moreover, it remains poorly understood how the autophagy activity is altered in astrocyte and whether the astrocytic autophagy dysfunction participates in PD development. It warrants intensive study. Recently, our group found that DRD2 receptor agonists, in addition to enhancing autophagy activity in DA neurons, also affect the autophagy processes in astrocytes. But This is limited to the in vitro study at the cellular level using the DRD2 receptor agonist/antagonist. Therefore, this project will investigate the potential role and molecular mechanism of DRD2 in regulating the autophagy activity in astrocytes, and define whether it is involved in the inhibition by DRD2 signaling on neuroinflammation using the astrocytic Atg7 conditional knockout mouse from the animal, cellular to molecular levels. The Research results will not only help to clarify the effect of DRD2 signaling on autophagy, and may also shed light on the regulation of astrocytic autophagy on neuroinflammation during PD progression. This may lead to a better understanding of PD pathogenesis from a new point of view.