Activin A影响脊膜源性的GABA能神经祖细胞在体分化的机制研究

脊髓损伤的治疗是医学领域的重大难题，其根本原因在于中枢神经系统的再生困难。损伤诱导的脊膜源性的GABA能神经祖细胞的出现和外源性信号分子激活素A（Activin A）的增高，为利用内源性修复机制提供了可能。但是这些内源性神经祖细胞的来源和在体分化的调控问题尚待解决。本项目拟以脊膜源性的GABA能神经祖细胞为切入点，以GAD67-GFP和GAD67-Cre转基因小鼠为主要研究工具，借助逆转录病毒标记、神经形态学、发育神经生物学等方法，探索脊膜源性的GABA能神经祖细胞的组织起源，并进一步观察其在体分化特点。同时，综合利用分子生物学和行为药理学等方法，深入分析Activin A对脊膜源性的GABA能神经祖细胞在体分化的影响和对脊髓损伤修复的影响。我们期望在初步阐明Activin A参与脊膜源性的GABA能神经祖细胞在体分化的机制同时，为脊髓损伤后神经修复和功能恢复提供新的思路和策略。

After the spinal cord injury, nerve regeneration is a major problem in the medical field. Glutamate excitotoxicity plays an important role in spinal cord injury, while enhanced the function of γ-aminobutyric acid (GABA) ergic neurons can effectively against excitotoxicity, and thus play a protective role. With the appearance of injury induced meninges-derived GABAergic progenitor cells and the increase of exogenous molecules Activin A after the spinal cord injury, it is possible for us to utilize of endogenous neurogenesis. However, these meninges-derived GABAergic progenitor cells originated in the nerve tissue or mesenchymal tissue has remained largely unknown, and it is not clear about the differentiation mechanisms of these meninges-derived GABAergic progenitor cells. In order to better understand the nerve regeneration, it is necessary to know the in vivo differentiation of the meninges-derived GABAergic progenitor cells. In this study, we will make all effort to clarify the in vivo differentiation of the meninges-derived GABAergic progenitor cells in cellular, organic and animal levels by using GAD67-GFP or GAD67-Cre transgenic mice, morphological, molecular biological, neurobiological and developmental methods. Meanwhile, the role of Activin A in the modulation of in vivo differentiation of meninges-derived GABAergic progenitor cells will also be investigated in this study. It is expected to offer more valuable information for the differentiation mechanisms of meninges-derived GABAergic progenitor cells and the establishment of therapeutic strategies for nerve regeneration after the spinal cord injury.