Defining and exploiting the plasticity transcriptome to repair the damaged spinal cord

摘要 一个世纪的研究表明，成人中枢神经系统在受伤或死亡后不能自我修复。 疾病。事实上，患有创伤性脊髓损伤的成年人保持着影响所有人的慢性功能缺陷 他们生活的方方面面。然而，越来越多的证据表明，成年中枢神经系统仍具有一定的启动能力 成长计划和职能重组，以应对活动、经历和轻微创伤 尤其是在强化康复治疗之后。在这项提案中，我们在体内使用了病毒跟踪 与FACS和单细胞RNA测序相结合开发一种全面的解剖和 成人皮质脊髓束(CST)分子图谱。我们计划利用这份图谱来定义分子 皮质脊髓束神经元特定亚群在康复过程中轴突生长的机制 轴突生长抑制因子NOGO受体-1的存在与缺失。我们相信，一个全面的 对启动和维持修复细胞介导的轴突生长的内在分子机制的理解 在CST定义的子集内，神经元然后可以被利用来设计新的治疗方法来修复急性 以及慢性损伤的脊髓。

SUMMARY A century of research has shown that the adult central nervous system is incapable of self-repair after injury or disease. Indeed, adults with traumatic spinal cord injuries maintain chronic functional deficits that impact all aspects of their lives. However, increasing evidence suggests that the adult CNS retains some ability to initiate a growth program and functionally re-organize in response to activity, experience and mild trauma and particularly after intensive rehabilitative therapy. In this proposal we have used in vivo viral tracing in combination with FACS and single cell RNA sequencing to develop a comprehensive anatomical and molecular atlas of the adult corticospinal tract (CST). We plan to leverage this atlas to define the molecular mechanisms that drive axon growth in specific subsets of corticospinal tract neurons during rehab in the presence and absence of the axon growth inhibitors nogo receptor-1. We believe that a comprehensive understanding of the intrinsic molecular mechanism that initiates and sustains rehab-mediated axon growth within defined subsets of CST neurons can then be exploited to design novel therapies to repair the acutely and chronically damaged spinal cord.