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再生外周轴突的光学刺激与电生理分析

Optical Stimulation and Electrophysiological Analysis of Regenerating Peripheral Axons.

作者信息

Ward Patricia J, English Arthur W

机构信息

Department of Cell Biology, Emory University School of Medicine, Atlanta, GA, USA.

出版信息

Bio Protoc. 2019 Jun 20;9(12). doi: 10.21769/BioProtoc.3281.

DOI:10.21769/BioProtoc.3281
PMID:31404384
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6688771/
Abstract

Although axons in the peripheral nervous system can regenerate, functional recovery after nerve injuries is poor. Activity-based therapies, such as exercise and electrical stimulation, enhance the regeneration of cut peripheral axons. Despite their effectiveness, clinical application of these experimental techniques has been limited. At least part of the basis for this translational barrier has been a lack of information as to the precise mechanism of activity-based therapies on peripheral axon regeneration. To evaluate the requirements for neuron-type specific activation to promote regeneration using these therapies, in the current protocol, we employed optogenetics. Utilizing the advantages of transgenic mouse lines we targeted opsin expression to different neuron types. Using fiber optics we activated those neurons with high temporal specificity as a model of activity-based intervention after nerve injury and to measure functional recovery achieved after such a treatment.

摘要

虽然外周神经系统中的轴突能够再生,但神经损伤后的功能恢复情况不佳。基于活动的疗法,如运动和电刺激,可促进切断的外周轴突再生。尽管这些疗法有效,但其临床应用一直有限。这种转化障碍的至少部分原因是缺乏关于基于活动的疗法对外周轴突再生的确切机制的信息。为了评估使用这些疗法促进再生所需的神经元类型特异性激活条件,在本实验方案中,我们采用了光遗传学方法。利用转基因小鼠品系的优势,我们将视蛋白的表达靶向不同的神经元类型。我们使用光纤以高时间特异性激活这些神经元,作为神经损伤后基于活动的干预模型,并测量这种治疗后实现的功能恢复情况。

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Angiogenesis is critical for the exercise-mediated enhancement of axon regeneration following peripheral nerve injury.血管生成对于运动介导的周围神经损伤后轴突再生的增强至关重要。
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Neuronal androgen receptor is required for activity dependent enhancement of peripheral nerve regeneration.神经元雄激素受体是活动依赖性增强周围神经再生所必需的。
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本文引用的文献

1
Chemogenetic Enhancement of Axon Regeneration Following Peripheral Nerve Injury in the SLICK-A Mouse.SLICK-A小鼠周围神经损伤后轴突再生的化学遗传增强
Brain Sci. 2018 May 22;8(5):93. doi: 10.3390/brainsci8050093.
2
Optogenetically enhanced axon regeneration: motor versus sensory neuron-specific stimulation.光遗传学增强轴突再生:运动神经元与感觉神经元特异性刺激。
Eur J Neurosci. 2018 Feb;47(4):294-304. doi: 10.1111/ejn.13836. Epub 2018 Feb 10.
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J Neural Eng. 2018 Feb;15(1):015002. doi: 10.1088/1741-2552/aa9126.
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Motoneuron activity is required for enhancements in functional recovery after peripheral nerve injury in exercised female mice.运动后的雌性小鼠外周神经损伤后功能恢复的增强需要运动神经元的活动。
J Neurosci Res. 2020 Mar;98(3):448-457. doi: 10.1002/jnr.24109. Epub 2017 Aug 3.
5
Optically-Induced Neuronal Activity Is Sufficient to Promote Functional Motor Axon Regeneration In Vivo.光诱导的神经元活动足以促进体内功能性运动轴突再生。
PLoS One. 2016 May 6;11(5):e0154243. doi: 10.1371/journal.pone.0154243. eCollection 2016.
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Combined Optogenetic and Chemogenetic Control of Neurons.神经元的光遗传学和化学遗传学联合控制
Methods Mol Biol. 2016;1408:207-25. doi: 10.1007/978-1-4939-3512-3_14.
7
Inhibitory luminopsins: genetically-encoded bioluminescent opsins for versatile, scalable, and hardware-independent optogenetic inhibition.抑制性视蛋白:用于通用、可扩展且与硬件无关的光遗传学抑制的基因编码生物发光视蛋白。
Sci Rep. 2015 Sep 24;5:14366. doi: 10.1038/srep14366.
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Strategies to promote peripheral nerve regeneration: electrical stimulation and/or exercise.促进周围神经再生的策略:电刺激和/或运动。
Eur J Neurosci. 2016 Feb;43(3):336-50. doi: 10.1111/ejn.13005. Epub 2015 Aug 14.
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Optogenetic control of nerve growth.神经生长的光遗传学控制
Sci Rep. 2015 May 18;5:9669. doi: 10.1038/srep09669.
10
Brief electrical stimulation improves nerve regeneration after delayed repair in Sprague Dawley rats.短暂电刺激可改善延迟修复后 Sprague Dawley 大鼠的神经再生。
Exp Neurol. 2015 Jul;269:142-53. doi: 10.1016/j.expneurol.2015.03.022. Epub 2015 Apr 2.