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Regenerative mechanisms of somatosensory neurons

体感神经元的再生机制

基本信息

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
项目类别：
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

项目摘要

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.

项目总结/文摘