Regenerative mechanisms of somatosensory neurons

体感神经元的再生机制

• 批准号: 10666969
• 负责人: Helen Lai
• 金额: $ 24.6万
• 依托单位: UT SOUTHWESTERN MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-03-01 至 2025-02-28
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10666969
• 关键词: Adult; Affect; Afferent Neurons; Alleles; Area; Autocrine Communication; Axon; Cell Lineage; Cell Proliferation; Cell Survival; Cell secretion; Cells; Central Nervous System; Classification; Degenerative Disorder; Development; Distal; Enterobacteria phage P1 Cre recombinase; Exploratory/Developmental Grant; Foundations; Future; Generations; Genetic; Goals; Growth Factor; Hippocampus; IGF2 gene; Injury; Insulin-Like Growth Factor II; Label; Link; Literature; Macrophage; Mus; Natural regeneration; Nerve Crush; Nerve Degeneration; Neural Crest; Neuroglia; Neurons; Paracrine Communication; Peripheral Nervous System; Peripheral nerve injury; Population; Process; Proliferating; Property; Role; Sensory; Signal Transduction; Source; Spinal Ganglia; Structure of choroid plexus; System; Testing; Therapeutic; adult neurogenesis; adult stem cell; axon regeneration; cell type; experimental study; gain of function; in vivo; insight; loss of function; mouse model; nerve injury; nerve stem cell; neurogenesis; neuron development; neuron regeneration; neuronal cell body; neuronal growth; neuronal survival; novel; progenitor; regenerative; research study; sciatic nerve; somatosensory; stem cells; stem-like cell; success; therapy development; timeline; tool; transcription factor; treatment strategy

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.

项目概要/摘要 成体神经干细胞在哺乳动物中枢神经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，表达一种可影响感觉神经元存活的生长因子 以及培养系统中的轴突再生以及通过外源性应用于受损神经。然而， 该生长因子的内源性来源尚不清楚。我们对这种新型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。我们建议检查该函数 这种生长因子对幼稚和损伤情况下的感觉神经元活力以及损伤后的轴突再生的影响 通过功能丧失和功能获得小鼠模型造成的损伤。此外，我们有理由相信细胞 表达这种生长因子的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 成人神经发生是否发生在 DRG 的证据。我们将检查神经元是否重新填充 损伤后的DRG，哪些类型的DRG细胞在损伤后长期增殖，以及损伤后是否增殖 取决于这个生长因子。此外，我们将开发遗传工具来追踪稀疏的谱系 表达该生长因子的细胞类型。这些目标的成功将为信号传递是否提供证据 应探索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、轴突再生甚至神经元再生的治疗策略 周围神经损伤后或退行性疾病中的体感神经元。