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In vitro priming response in dorsal root ganglia partially mimics injury-driven pre-conditioning response and reprograms neurons for enhanced outgrowth
Molecular and Cellular Neuroscience ( IF 2.6 ) Pub Date : 2020-11-25 , DOI: 10.1016/j.mcn.2020.103573
Anand Krishnan 1 , Shubham Dwivedi 2 , Ambika Chandrasekhar 3 , Aparna Areti 3 , Douglas W Zochodne 3
Affiliation  

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.



中文翻译:

背根神经节的体外启动反应部分模拟了损伤驱动的预处理反应,并重新编程神经元以促进生长

周围神经损伤有可能导致个人长期残疾。修复神经损伤的主要问题是轴突生长速度慢。尽管一些分子已被确定为改善轴突生长的潜在候选者,但它们在临床实践中的潜在转化是初步的,并且在很大程度上尚未得到探索。这需要确定其他具有改善轴突生长潜力的候选分子。缺乏简单的非手术筛选模型也给快速筛选潜在的候选分子带来了障碍。在这项工作中,我们开发了一种新颖的、快速的神经再生疗法筛选模型,该模型仍专注于成人神经元。该模型涉及在解离前 24 小时内对感觉神经节进行简单的孵化。出奇,该模型具有独特的事件,可重新编程感觉神经元并支持有利于轴突生长的神经胶质细胞。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感觉神经节中经典的轴突切开引起的变化。总体而言,该模型提供了一个平台,该平台不仅允许快速筛选候选药物,而且为研究神经元和神经胶质细胞中旨在提高轴突生长速度的新型内在分子变化提供了机会。

更新日期:2020-12-11
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