Signaling mechanisms for astrocyte polarization during glial scar formation after spinal cord injury

脊髓损伤后胶质疤痕形成过程中星形胶质细胞极化的信号机制

基本信息

批准号：
9401902
负责人：
YIMIN ZOU
金额：
$ 23.25万
依托单位：
UNIVERSITY OF CALIFORNIA, SAN DIEGO
依托单位国家：
美国
项目类别：
财政年份：
2017
资助国家：
美国
起止时间：
2017-05-01 至 2019-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9401902
关键词：
Adult Animals Apical Astrocytes Axon Chondroitin Sulfate Proteoglycan Cicatrix Cues Demyelinations Drosophila genus Employee Strikes Epithelial Evolution Fibroblasts Genes Glial Fibrillary Acidic Protein Gliosis Growth Growth Cones Hair Inflammation Inflammatory Injury Knock-out Knockout Mice Laboratories Labyrinth Lesion Mammals Mediating Morphology Motor Myelin Natural regeneration Neuraxis Oligodendroglia Pathway interactions Process Proliferating Proteins Role STAT3 gene Sensory Signal Pathway Signal Transduction Site Spinal Cord Spinal cord injury Testing Therapeutic Tissues axon growth axon guidance axon injury axon regeneration cell motility cell type convergent extension dorsal column gastrulation inhibitor/antagonist metallothionein III planar cell polarity relating to nervous system repaired response response to injury

项目摘要

Spinal cord injury (SCI) can result in long-term loss of sensory and motor functions due to axon damage, gliosis, inflammation, and demyelination. Transected axons fail to regenerate in the adult mammalian CNS due to 1) lack of intrinsic regrowth ability, 2) inhibitory extrinsic cues including myelin associated proteins and chondroitin sulfate proteoglycans enriched in the glial scar as well as axon guidance molecules and 3) a physical gap of neural tissue for axon growth. Astrocytes constitute one of the principal components of the glial scar. In response to SCI, astrocytes become reactivated and start proliferation. How astrocyte reactivation is initiated and what cellular signaling pathways are involved in astrocyte polarization is largely unknown. Therefore, we hypothesize that Wnt/PCP signaling may be an important regulator of polarization of the reactive astrocytes after spinal cord injury, which may be important for glial scar formation and glial bridge formation.

脊髓损伤 (SCI) 可因轴突损伤而导致感觉和运动功能长期丧失，神经胶质增生、炎症和脱髓鞘。由于成年哺乳动物中枢神经系统被切断的轴突无法再生 1) 缺乏内在的再生能力，2) 抑制性外在信号，包括髓磷脂相关蛋白和富含神经胶质疤痕的硫酸软骨素蛋白多糖以及轴突引导分子和3)a 用于轴突生长的神经组织的物理间隙。星形胶质细胞构成神经胶质疤痕的主要成分之一。作为对 SCI 的反应，星形胶质细胞重新激活并开始增殖。星形胶质细胞的再激活是如何启动的以及星形胶质细胞极化涉及哪些细胞信号通路在很大程度上尚不清楚。因此，我们推测Wnt/PCP信号可能是脊髓损伤后反应性星形胶质细胞极化的重要调节因子，这对于神经胶质疤痕形成和神经胶质桥形成可能很重要。