OPC分泌Wnt信号调控星形胶质网络形成及其在精神行为中的作用和机制

近年来，胶质细胞因在神经环路建立及脑功能中的重要作用而备受关注，但胶质细胞间相互作用，尤其是少突胶质细胞对星形胶质细胞（AST）网络的调控作用及相关机制还缺乏认识。基于前期工作和预实验发现，我们提出以下研究假说：少突胶质细胞前体细胞（OPC）可能通过释放Wnt信号分子调控AST胶质网络的发育，参与脑功能活动。我们拟利用DTA小鼠（ROSA26-eGFP-DTA），制备能特异性诱导OPC死亡，并能标记AST的三转基因小鼠，结合形态学、电生理及行为学等多种技术开展以下研究：（1）明确OPC对AST分化成熟及胶质网络建立的作用及其对神经精神行为的影响；（2）探讨OPC是否通过分泌Wnt7激活AST的Wnt通路，调控胶质网络的发育；（3）观察调控AST的Wnt激活对OPC缺失小鼠神经精神行为的改善。以上研究问题的回答将有助于阐明OPC调控AST网络形成及其在脑的神经精神行为发育中的作用和机制。

Increasing evidence has shown the involvement of glial cells in establishing neural circuitry and brain functions. However, the interaction between different cell types of glial cells in CNS, especially how the development of the astroglial network is regulated by oligodendroglial cells remains unclear. Based on our previous work and preliminary data, we hypothesize that oligodendrocyte precursor cell (OPC) could regulate the establishment and maturation of the astroglial network by Wnt signals derived from OPC. We will develop the triple transgenic mouse (PDGFRαCREERT2: DTA: Aldh1L1-GFP) in which OPCs are eliminated and astrocytes and label. By utilizing morphological and physiological approaches, along with behavioral test, we aim to investigate: (1) The role of OPCs in the development of astrocyte and the establishment of astroglial network. Whether neuropsychic behavioral disorders are a consequence of the abnormal astroglial network caused by the elimination of OPCs; (2) Whether OPC derived Wnt7a/b is the key pathway that activates the Wnt signaling which is important for astroglial network formation; (3) Whether modulating of Wnt signaling in astrocytes can improve the behavioral disorders caused by OPC elimination during postnatal brain development. Together, this project will provide new insight into how OPCs could be involved in the establishment of astroglial network and brain function development.