The Role of Perineurial Glia in PNS Regeneration

描述（由申请人提供）：外周神经系统（PNS）在中枢神经系统（CNS）和身体之间起到传递信息的基本功能。这些信息以电信号的形式传递，沿着PNS神经元的轴突向下传播。当周围神经受伤时，中枢神经系统和组织之间的联系被切断，导致感觉和运动控制丧失。PNS损伤是常见的，尽管这些神经能够再生，但患者通常不能恢复完全的功能。完整的神经是由被几层鞘胶质细胞和结缔组织包围的轴突组成的。再生需要这些层中的所有细胞精确地协调它们的行为，以确保碎片被清除，新的轴突重新生长。轴突被雪旺细胞包裹，雪旺细胞被神经内膜、神经周围膜和神经外膜包裹。会神经膜是神经功能所必需的保护性细胞鞘，由扁平的、交错的会神经胶质细胞组成。这些细胞在神经发育中起着至关重要的作用，但它们如何对神经损伤作出反应并参与再生尚不清楚。本项目的长期目标是阐明神经周围胶质细胞在PNS再生中的作用。这将通过使用一种新的损伤试验来研究，该试验旨在观察活体神经横断后单个胶质细胞的动态行为。在这个实验中，a

DESCRIPTION (provided by applicant): The peripheral nervous system (PNS) serves the essential function of relaying information between the central nervous system (CNS) and the body. This information is transmitted in the form of electrical signals, which travel down the axons of PNS neurons. When peripheral nerves become injured, the connection between the CNS and tissues is severed, causing sensation and motor control to be lost. PNS injuries are common, and although these nerves are capable of regenerating, patients often do not regain full functional recovery. The complete nerve is formed of axons surrounded by several layers of ensheathing glia and connective tissue. Regeneration requires all the cells in these layers to precisely coordinate their behaviors to ensure debris is cleared and new axons re-grow. Axons are wrapped by Schwann cells, which are then surrounded by an endoneurium, perineurium, and epineurium. The perineurium is a protective cellular sheath essential for nerve function, and is formed by flattened, interdigitated perineurial glial cells. These cells play an essential role n nerve development, but how they respond to nerve injury and participate in regeneration is not known. The long-term goal of this project is to elucidate the role of perineurial glia in PNS regeneration. This will be investigated through use of a novel injury assay designed to view the dynamic behaviors of individual glial cells following a nerve transection in vivo. In this assay, a Micropoint laser ablation system is used to transect the motor nerve in live, transgenic zebrafish, and the behaviors perineurial glia are visualized using time-lapse confocal microscopy. Preliminary data from this assay suggests that perineurial glia send membrane processes toward injury sites, form bridges between divided proximal and distal nerve stumps, and may aid in phagocytizing debris. This will be investigated further by: 1) Fully characterizing the perineurial glial response to nerve injury, and how this response is coordinated with Schwann cells and macrophages through the use of vital dyes, immunohistochemistry, and in vivo imaging, 2) Investigating if axonal damage is the cue that initiates perineurial glial injury responses using in vivo imaging, genetic mutants, and injections of degenerating axonal material, and 3) Using genetic manipulation to determine if perineurial glia are essential for nerve degeneration and regeneration. This work will lead to a more complete understanding of how multiple cell types coordinate their actions to rebuild the nervous system after disease or injury.