Mechanisms of glial bridging and neurogenesis during spinal cord regeneration in zebrafish

斑马鱼脊髓再生过程中胶质桥接和神经发生的机制

• 批准号: 10676170
• 负责人: Mayssa H. Mokalled
• 金额: $ 38.84万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-09-30 至 2024-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10676170
• 关键词: Adult; American; Astrocytes; Cells; Cicatrix; Coupled; Data; Dorsal; Functional Regeneration; GDF8 gene; Gene Expression Profile; Genes; Genetic; Gliosis; Growth; Human; Impairment; In Situ Hybridization; Inflammatory; Injury; Intervention; Mammals; Modeling; Molecular; Motor; Muscle; Natural regeneration; Nervous System; Neuroglia; Neurons; Outcome; Paralysed; Process; Publishing; Radial; Recovery; Recovery of Function; Regenerative Medicine; Regenerative capacity; Regulatory Element; Rehabilitation therapy; Sensory; Signal Pathway; Signal Transduction; Spinal Cord; Spinal Cord Lesions; Spinal Cord transection injury; Spinal Manipulation; Spinal cord damage; Spinal cord injury; Supporting Cell; Testing; Therapeutic; Tissues; Transgenic Organisms; Work; Zebrafish; adult neurogenesis; connective tissue growth factor; deep sequencing; defined contribution; extracellular; factor A; functional disability; innovation; loss of function; member; mutant; nerve stem cell; neural; neurogenesis; neuron loss; neuron regeneration; neurotoxic; neurotoxicity; pharmacologic; premature; psychologic; regeneration function; regenerative; repaired; response; self-renewal; severe injury; spinal cord regeneration; spinal cord repair; stem cells; teleost fish; therapy development

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 (SC) transection. Following SCI, adult zebrafish initiate a glial bridge that reconnects the severed SC, and regenerate functional neurons that contribute to SC repair. Pro-regenerative glial bridging and efficient adult neurogenesis distinguish the zebrafish SC from the mammalian SC and enable natural repair post-injury. Importantly, these pro-regenerative processes occur without the detrimental outcomes of reactive gliosis or neurotoxicity elicited by the mammalian SC. However, little is known about the cellular and molecular mechanisms that direct glial bridging or neurogenesis in zebrafish. In this proposal, we will 1) investigate the signaling pathways that direct glial bridging, 2) identify a new regulator of neurogenesis, and 3) identify the progenitor cells that give rise to bridging glia or regenerating neurons after SCI. This study will provide mechanistic understanding of glial bridging and neurogenesis during zebrafish SC regeneration, and will guide approaches for manipulating SCI outcomes in mammals.

每年约有18,000名美国人遭受新的脊髓损伤（SCI）。初级和次要赔偿 由SCI引起的永久性感觉和运动功能，需要长期治疗， 康复和心理干预措施。因此，开发治疗或反向SCI的疗法是一种压力 再生医学的需求。与哺乳动物相反，硬骨鱼自然再生功能神经 完整的脊髓（SC）横断性后组织和反向瘫痪。在SCI之后，成年斑马鱼开始 重新连接切断的SC并再生有助于SC修复的功能神经元的神经胶桥。 亲胶质桥接和有效的成年神经发生，将斑马鱼SC与 哺乳动物SC并实现自然修复后伤害。重要的是，这些促进过程发生 没有哺乳动物SC引起的反应性神经胶质或神经毒性的有害结果。然而， 关于直接在神经胶质桥接或神经发生的细胞和分子机制知之甚少 斑马鱼。在此提案中，我们将1）研究直接神经桥桥的信号传导途径，2）确定 神经发生的新调节剂，以及3）确定产生桥接神经胶质或再生的祖细胞 科学后的神经元。这项研究将提供对神经胶质桥接和神经发生的机械理解。 斑马鱼SC的再生，并将指导操纵哺乳动物的SCI结果的方法。

项目成果

Spinal Cord Injury and Assays for Regeneration.

脊髓损伤和再生测定。

• DOI: 10.1007/978-1-0716-3401-1_14
• 发表时间: 2024
• 期刊: Methods in molecular biology (Clifton, N.J.)
• 作者: Burris,Brooke;Mokalled,MayssaH
• 通讯作者: Mokalled,MayssaH

Myostatin is a negative regulator of adult neurogenesis after spinal cord injury in zebrafish.

• DOI: 10.1016/j.celrep.2022.111705
• 发表时间: 2022-11-22
• 期刊: Cell reports
• 影响因子: 8.8