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在体背根神经节的初步反应部分模拟了损伤驱动的预处理反应,并为增强神经突生长重新编程神经元。

In vitro priming response in dorsal root ganglia partially mimics injury-driven pre-conditioning response and reprograms neurons for enhanced outgrowth.

机构信息

Division of Neurology, Department of Medicine, and the Neuroscience and Mental Health Institute, University of Alberta, Edmonton, Alberta, Canada; Dept. of Anatomy, Physiology, and Pharmacology, College of Medicine, University of Saskatchewan, Canada; Cameco MS Neuroscience Research Centre, Saskatoon, Saskatchewan, Canada.

Dept. of Anatomy, Physiology, and Pharmacology, College of Medicine, University of Saskatchewan, Canada; Cameco MS Neuroscience Research Centre, Saskatoon, Saskatchewan, Canada.

出版信息

Mol Cell Neurosci. 2021 Jan;110:103573. doi: 10.1016/j.mcn.2020.103573. Epub 2020 Nov 25.

Abstract

Peripheral nerve injuries have the potential to bring about long-term disabilities in individuals. The major issue in repairing nerve injuries is the poor growth rate of axons. Although several molecules have been identified as potential candidates for improving axon growth, their potential translation into clinical practice is preliminary and largely unexplored. This necessitates identifying additional molecular candidates with superior potential to improve axon growth. Lack of a simple non-surgical screening model also poses a hurdle in rapidly screening potential candidate molecules. In this work, we developed a novel, rapid screening model for nerve regeneration therapeutics that retains a focus on adult neurons. The model involves simple incubation of sensory ganglia over a period of 24 h prior to dissociation. Surprisingly, this model features unique events that reprogram both sensory neurons and supporting glia favoring axon growth. Moreover, several associated cellular and molecular changes involved in this model partially mimic classic axotomy-induced changes in sensory ganglia. Overall, this model presents with a platform that not only allows rapid screening of drug candidates but offers opportunities in studying novel intrinsic molecular changes in both neurons and glial cells directed towards improving the pace of axon growth.

摘要

周围神经损伤有可能给个体带来长期残疾。修复神经损伤的主要问题是轴突的生长速度缓慢。尽管已经确定了几种分子作为潜在的候选物来改善轴突生长,但它们在临床上的应用潜力还处于初步阶段,在很大程度上尚未得到探索。因此,需要确定具有更好改善轴突生长潜力的其他分子候选物。缺乏简单的非手术筛选模型也给潜在候选分子的快速筛选带来了障碍。在这项工作中,我们开发了一种新的、快速的神经再生治疗筛选模型,该模型仍然专注于成年神经元。该模型涉及在分离前将感觉神经节简单孵育 24 小时。令人惊讶的是,该模型具有独特的事件,可重新编程感觉神经元和支持性神经胶质细胞,有利于轴突生长。此外,该模型中涉及的几种相关细胞和分子变化部分模拟了经典的感觉神经节损伤诱导变化。总的来说,该模型提供了一个平台,不仅可以快速筛选药物候选物,还为研究神经元和神经胶质细胞中改善轴突生长速度的新型内在分子变化提供了机会。

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