Regenerative mechanisms of somatosensory neurons

项目总结/摘要 成体神经干细胞在哺乳动物中枢神经系统的离散区域产生新形成的神经元 系统成人神经发生是否发生在周围神经系统尚不清楚。我们发现了一个稀疏的细胞 背根神经节（DRG）中的一种类型，表达一种影响感觉神经元存活的生长因子 以及通过外源性应用于损伤的神经而在培养系统中进行轴突再生。但 该生长因子的内源性来源未知。我们对这种新细胞类型的发现表明， DRG本身就是这种生长因子的来源。我们将在目标1中测试这个想法。我们建议检查函数 这种生长因子对感觉神经元活力在幼稚和损伤的情况下和轴突再生后 通过功能丧失和功能获得小鼠模型的损伤。另外，我们有理由相信 表达这种生长因子的细胞类型也可能具有成体干细胞样特性。在目标2中，我们将提供 成年神经发生是否发生在DRG的证据。我们将研究神经元是否重新填充了 伤后DRG，伤后长期何种类型的DRG细胞增殖，伤后是否增殖 这取决于这个增长因素。此外，我们将开发遗传工具， 表达这种生长因子的细胞类型。这些目标的成功将提供证据， 通过这种生长因子或通过稀疏DRG细胞类型分泌生长因子 作为支持DRG细胞活力、轴突再生和可能的神经元再生的治疗策略 周围神经损伤或退行性疾病后的体感神经元。

Project Summary/Abstract Adult neural stem cells give rise to newly formed neurons in discrete areas of the mammalian central nervous system. Whether adult neurogenesis occurs in the peripheral nervous system is unclear. We found a sparse cell type in the dorsal root ganglion (DRG) that expresses a growth factor shown to affect sensory neuronal survival and axonal regeneration in culture systems and by exogenous application to injured nerves. However, the endogenous source of this growth factor was unknown. Our discovery of this novel cell type suggests that the DRG itself is the source for this growth factor. We will test this idea in Aim 1. We propose to examine the function of this growth factor on sensory neuron viability in both naïve and injury contexts and axonal regeneration after injury through both loss and gain-of-function mouse models. In addition, we have reason to believe that the cell type expressing this growth factor may also have adult stem cell-like properties. In Aim 2, we will provide evidence for whether adult neurogenesis occurs in the DRG. We will examine whether neurons repopulate the DRG after injury, what types of DRG cells proliferate after injury long-term, and whether proliferation after injury is dependent on this growth factor. In addition, we will develop genetic tools to follow the lineage of the sparse cell type expressing this growth factor. Success in these Aims will provide evidence as to whether signaling through this growth factor or secretion of the growth factor through the sparse DRG cell type should be explored as a therapeutic strategy to support DRG cell viability, axonal regeneration, and perhaps neuronal regeneration of somatosensory neurons after peripheral nerve injury or in degenerative diseases.