Balancing degeneration and regeneration in the echinoderm nervous system

平衡棘皮动物神经系统的退化和再生

基本信息

批准号：
9435194
负责人：
JOSE E GARCIA-ARRARAS
金额：
$ 22.35万
依托单位：
UNIVERSITY OF PUERTO RICO RIO PIEDRAS
依托单位国家：
美国
项目类别：
财政年份：
2017
资助国家：
美国
起止时间：
2017-09-15 至 2019-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9435194
关键词：
Adult Affect Amaze Animals Apoptosis Biological Models Caenorhabditis elegans Cell Death Cell Proliferation Cell division Cell physiology Cells Cellular biology Communities Comparative Study Complex Data Databases Development Drosophila genus Elderly Electroporation Emotional Equilibrium Event Family Future Gene Expression Gene Expression Profile Genes Genomics Goals Health Services Holothuria Human Immunology Impairment In Vitro Individual Injury Life Mammals Mediating Messenger RNA Molecular Mus Natural regeneration Nerve Degeneration Nerve Regeneration Nervous system structure Neuraxis Neurodegenerative Disorders Neuroglia Organism Outcome Pharmaceutical Preparations Pharmacology Phylogenetic Analysis Play Population Process Protocols documentation RNA Interference Radial Rattus Regenerative response Research Rest Role Sea Cucumbers Signal Pathway Signal Transduction Societies Structure of radial nerve System Technology Tissues Vertebrates WNT Signaling Pathway Wound Healing base cell dedifferentiation comparative differential expression economic impact experimental study improved in vivo knock-down loss of function neurogenesis novel novel therapeutics regenerative repaired tool transcriptome transcriptome sequencing treatment effect

项目摘要

Abstract The capacity to regenerate the central nervous system of adult mammals, including humans, is highly limited. This is why loss of functions, following injuries or neurodegenerative diseases, impair the organisms for the rest of their life. In contrast to mammals, other animals have various degrees of regenerative abilities. Among deuterostomes, echinoderms are known for their amazing repair and regeneration mechanisms. This proposal uses an echinoderm, as a novel model system, to study nervous system regeneration. This organism, the sea cucumber Holothuria glaberrima, possesses the innate ability to regenerate components of its central nervous system following injury or autotomy. The present proposal searches to establish the role that three cellular mechanisms (cell dedifferentiation, cell proliferation and cell death) play in the balance between degeneration and regeneration. Cellular mechanisms will be analyzed using pharmacological and molecular tools. The experimental strategy takes advantage of a recently established culture system for nervous system explants and on the ability to trigger dedifferentiation by electroporation. Additional experiments are aimed at identifying the underlying molecular bases of nervous system regeneration. The gene expression profile of normal and regenerating nervous components will be compared and used to identify the genes associated with the process of nervous system regeneration. Our results could serve as the basis for the development of new therapeutics/drugs that modulate regenerative processes. They will also provide important information to other fields of research, including wound healing, immunology, cell biology, genomics and phylogenetics. Finally, the outcome of these experiments will bring us closer to a better understanding of regenerative processes in general.

抽象的包括人类在内的成年哺乳动物的中枢神经系统再生能力，是非常有限的。这就是为什么在受伤或神经退行性疾病后会丧失功能，损害有机体的余生。与哺乳动物相比，其他动物有不同程度的再生能力。在后口动物中，棘皮动物以他们惊人的修复和再生机制。该提案使用棘皮动物作为新颖的模型系统，用于研究神经系统再生。这种生物，海参海参 (Holothuria glaberrima) 具有再生其中枢成分的先天能力受伤或自残后的神经系统。本提案寻求建立三种细胞机制（细胞去分化、细胞增殖和细胞死亡）在退化和细胞之间的平衡中发挥作用再生。将使用药理学和分子工具分析细胞机制。该实验策略利用了最近建立的神经培养系统系统外植体和通过电穿孔触发去分化的能力。额外的实验旨在确定神经系统的潜在分子基础再生。正常和再生神经成分的基因表达谱将进行比较并用于鉴定与神经系统过程相关的基因再生。我们的结果可以作为开发新疗法/药物的基础调节再生过程。他们还将向其他领域提供重要信息研究，包括伤口愈合、免疫学、细胞生物学、基因组学和系统发育学。最后，这些实验的结果将使我们更进一步地了解一般的再生过程。