已知神经炎症是脑老化和中枢神经系统退行性疾病中普遍发生的现象。神经炎症对这些疾病的发生和发展有重要的贡献，但其分子和细胞机理尚不完全清楚。我们推测，脑内不同类型细胞间的通讯发生异常在神经炎症的发展进程中发挥重要的作用。本项目将从ALDH1L1阳性细胞入手，分析不同星形胶质细胞亚群之间以及与其它神经细胞之间的相互作用，鉴定这些相互作用对神经炎症的贡献；分析多巴胺D2受体—alphaB晶状体蛋白信号通路障碍引起星形胶质细胞功能改变的分子机理；寻找alphaB-晶状体蛋白可能的细胞膜表面受体，鉴定其在星形胶质细胞—小胶质细胞之间通讯的作用；探讨小胶质细胞的多巴胺受体亚型及Vav3在神经元—胶质细胞之间通讯的作用。本研究可加深对神经炎症状态下介导细胞间通讯的重要环节的了解，有望对神经炎症发生和发展的基础理论作出贡献，并为建立抑制神经炎症、缓解神经退行性疾病的方法提供理论基础。

Activated neuroglial cells contribute to immune deregulation and neuroinflammation, which are associated with ageing and a variety of neurodegenerative disorders. However, the molecular and cellular mechanisms underlying the regulation of innate immunity in the central nervous system remain elusive. It is hypothesized that alterations in cell-to-cell communication may contribute to the progression of neuroinflammation. We intend to study the role of ALDH1L1-positive astrocytes in the regulation of neuroinflammation and to determine whether communications between this group of cells and other subpopulations of astrocytes contributes to inflammatory responses. We will investigate the molecular mechanisms underlying dysfunction of astroglial dopamine D2 receptor – alphaB-crystallin signaling. Identification of putative alphaB-crystallin receptor will also be carried out and the role of this putative receptor in the astrocyte-to-microglia communications will be explored. Moreover, we will investigate whether microglial dopamine receptor subtypes and Vav3 mediate neuron-to-glial cell communications in MPTP-induced inflammatory response. Our study will improve our understanding on cell-to-cell communications in the neuroinflammatory process. Successful completion of proposed study will make important contribution to our understanding of molecular and cellular basis of neuroinflammation and will hopefully lay the foundations for future development of new therapeutic approaches against brain ageing and neurodegenerative diseases.