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.

抽象的再生包括人类在内的成年哺乳动物的中枢神经系统的能力，高度有限。这就是为什么在受伤或神经退行性疾病之后的功能丧失的原因，损害生物的余生。与哺乳动物相反，其他动物具有各种程度的再生能力。在氘抑制中，棘皮动物以他们惊人的维修和再生机制。该建议使用echinoderm作为新型模型系统，研究神经系统再生。这个有机体，海参 Holothuria glaberrima具有先天的重新生成的能力受伤或自动切开术后神经系统。目前的建议搜索以确定三种细胞机制的作用（细胞去分化，细胞增殖和细胞死亡）在变性和再生。将使用药理和分子工具分析细胞机制。实验策略利用了最近建立的神经培养系统系统外植体以及通过电穿孔触发去分化的能力。额外的实验旨在识别神经系统的基本分子碱基再生。正常和再生神经成分的基因表达谱将比较并用于识别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治疗剂/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加了解对总体上再生过程。