Glial cell responses promote spinal cord repair in zebrafish

胶质细胞反应促进斑马鱼脊髓修复

• 批准号: 10446788
• 负责人: Mayssa H. Mokalled
• 金额: $ 40.64万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-04-01 至 2027-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10446788
• 关键词: Adult; American; Astrocytes; Automobile Driving; CRISPR screen; Cells; Cellular biology; Chronic; Cicatrix; Environment; Functional Regeneration; Gene Expression; Genes; Genetic; Genetic Transcription; Gliosis; Grant; Human; Impairment; Injury; Intervention; Macrophage Activation; Mammals; Maps; Microglia; Molecular; Motor; Natural regeneration; Neuroglia; Outcome; Paralysed; Pathogenicity; Pathway interactions; Protein Isoforms; Recovery; Recovery of Function; Regenerative Medicine; Regenerative capacity; Regenerative response; Rehabilitation therapy; Reporter; Resolution; Role; Scientist; Sensory; Series; Spinal Cord; Spinal Cord transection injury; Spinal cord injury; Structure; Testing; Therapeutic; Tissues; Transcription Repressor; Work; Zebrafish; epithelial to mesenchymal transition; experimental study; extracellular; fascinate; gain of function; gene regulatory network; in vivo; innovation; loss of function; macrophage; mutant; neural repair; overexpression; peptidomimetics; progenitor; programs; psychologic; regeneration model; regenerative; regenerative cell; relating to nervous system; response; response to injury; spinal cord regeneration; spinal cord repair; teleost fish; therapy development; transcription factor; transcriptomics

ABSTRACT Around 18,000 Americans suffer new spinal cord injuries (SCI) each year. Primary and secondary damages caused by SCI permanently impair sensory and motor functions, which require long-term therapeutic, rehabilitative, and psychological interventions. Thus, developing therapies to treat or reverse SCI is a pressing need in regenerative medicine. In contrast to mammals, teleost fish naturally regenerate functional neural tissue and reverse paralysis after complete spinal cord transection. Although innate spinal cord repair in zebrafish has fascinated scientists for decades, the contribution of glial cells to this elevated regenerative capacity is vastly understudied. Following SCI, adult zebrafish initiate a glial bridge that reconnects the severed spinal cord and supports functional neural repair. Pro-regenerative glial bridging distinguishes the zebrafish spinal cord and occurs without the detrimental outcomes of reactive gliosis elicited by the mammalian spinal cord. We propose that zebrafish glia orchestrate a series of transient, pro-regenerative responses that enable spinal cord repair. In this proposal, we will 1) determine the early injury responses that initiate glial bridging, 2) identify glial bridging mechanisms that are specific to zebrafish bridging glia and absent in mammalian glia, and 3) uncover the cellular and molecular mechanisms that direct glial bridge disassembly after regeneration is complete. This study will provide a mechanistic understanding of glial cell biology during zebrafish spinal cord regeneration, and will guide approaches for manipulating glial cells to promote spinal cord repair in mammals.

摘要