微管相关蛋白伴侣蛋白PACSIN1在调控周围神经再生放大极限中的作用机制研究

Following peripheral nerve injury, especially in root avulsion, the effect of repair is still far from satisfactory. Lack of sufficient number of sources from donor nerves is one of the bottlenecks that affect nerve regeneration and functional compensation. We found in previous studies that there is compensatory phenomenonof collateral sprouts during axons regeneration. The amplifying limit of the collateral sprout is 3.3 times. And the results inanimal experiments indicated that the use of collateral sprouts was helpful for recovery of neurological function from an intact nerve to repair a nearby nerve. PACSIN1 is a binding partner of Tau protein, which regulatesaxon microtubule dynamics and reshaping. Previous studies in vitro experiments suggest that block of PACSIN1 protein in dorsal root ganglion neurons cells can increase its number of collateral sprouts of axons, but does not affect the nerve regeneration. In the present studies, a series of experiments will be designed in rats in vivo and in vitro. These studies will investigate the effect of inhibition of PACSIN1 protein on improvement of amplifying limit of collateralsduring axons regeneration and reduction of the sources of donor nerve. It would provide important significance in promotingrepairing effectof nerve trunk and in minimizing the dysfunction of donor nerve fiber in clinic.

周围神经损伤，尤其是高位根性撕脱伤，修复的效果仍然差强人意。缺乏足够数量的供体神经来源，是影响神经再生与功能代偿的瓶颈之一。本课题组前期研究发现，周围神经轴突再生过程中存在放大效应，其放大极限是3.3倍；同时在动物实验证实，利用神经放大效应，用细小神经可以部分代偿损伤的粗大神经的功能。PACSIN1是调控轴突微管动态性和重塑性的Tau结合伴侣蛋白。前期的体外实验提示，阻断背根神经元细胞的PACSIN1蛋白，可以增加其再生轴芽的数量，且不影响神经的再生。但PACSIN1蛋白在体内神经损伤修复过程中是否有类似的增强再生轴芽的放大效应? 目前尚不明确。本研究将设计系列实验，在大鼠体内外探讨调控PACSIN1蛋白能否提高轴突再生的放大极限，是否可减少供体神经的来源，促进功能的恢复。这对于促进损伤的粗大神经的修复，并尽可能减少供区的功能障碍具有重要的科学意义和临床价值。

周围神经损伤，尤其是高位根性撕脱伤，修复的效果仍然差强人意。缺乏足够数量的供体神经来源，是影响神经再生与功能代偿的瓶颈之一。本课题组前期研究发现，周围神经轴突再生过程中存在放大效应，其放大极限是3.3倍；同时在动物实验证实，利用神经放大效应，用细小神经可以部分代偿损伤的粗大神经的功能。PACSIN1是调控轴突微管动态性和重塑性的Tau结合伴侣蛋白。前期的体外实验提示，阻断背根神经元细胞的PACSIN1蛋白，可以增加其再生轴芽的数量，且不影响神经的再生。但PACSIN1蛋白在体内神经损伤修复过程中是否有类似的增强再生轴芽的放大效应? 目前尚不明确。本研究将设计系列实验，在大鼠体内外探讨调控PACSIN1蛋白能否提高轴突再生的放大极限，是否可减少供体神经的来源，促进功能的恢复。这对于促进损伤的粗大神经的修复，并尽可能减少供区的功能障碍具有重要的科学意义和临床价值。