Proper wiring of newborn neurons to control bladder function after complete spinal cord injury
Proper wiring of newborn neurons to control bladder function after complete spinal cord injury
复制标题
新生神经元的正确连接以控制脊髓完全损伤后的膀胱功能
DOI：
10.1016/j.biomaterials.2022.121919
复制
发表时间：
2022-11-28
期刊：
影响因子：
14
通讯作者：
Li, Xiaoguang
中科院分区：
文献类型：
--
作者：
Hao, Fei;Jia, Fan;Li, Xiaoguang
通过生物活性材料激活内源性神经发生，能够通过形成新的中继神经回路恢复完全脊髓损伤（SCI）后的感觉/莫尔功能。在成年中枢神经系统（CNS）新生神经元的潜在布线逻辑是未知的。在这里，我们报告神经营养素3加载壳聚糖生物材料基本上恢复SCI后的膀胱功能。利用伪狂犬病病毒（PRV）、狂犬病病毒（RV）和顺行腺相关病毒（AAV）的多种神经回路追踪技术证实，新生神经元整合到排尿神经回路中，并重新连接高级脑中心和低级脊髓中心以控制排尿，并参与下尿路功能的恢复，即使在没有长距离轴突再生的情况下。光遗传学和化学遗传学研究进一步支持脊髓上控制下尿路功能部分恢复的观点。我们的数据表明，再生的中继神经元可以适当地整合到中断的远程神经回路，以恢复成年中枢神经系统的功能。
Activation of endogenous neurogenesis by bioactive materials enables restoration of sensory/mor function after complete spinal cord injury (SCI) via formation of new relay neural circuits. The underlying wiring logic of newborn neurons in adult central nervous system (CNS) is unknown. Here, we report neurotrophin3-loaded chitosan biomaterial substantially recovered bladder function after SCI. Multiple neuro-circuitry tracing technologies using pseudorabies virus (PRV), rabies virus (RV), and anterograde adeno-associated virus (AAV), demonstrated that newborn neurons were integrated into the micturition neural circuits and reconnected higher brain centers and lower spinal cord centers to control voiding, and participated in the restoration of the lower urinary tract function, even in the absence of longdistance axonal regeneration. Opto- and chemo-genetic studies further supported the notion that the supraspinal control of the lower urinary tract function was partially recovered. Our data demonstrated that regenerated relay neurons could be properly integrated into disrupted long-range neural circuits to restore function of adult CNS.