Bioluminescent Optogenetics: A Novel Experimental Therapy to Promote Axon Regeneration after Peripheral Nerve Injury.
Bioluminescent Optogenetics: A Novel Experimental Therapy to Promote Axon Regeneration after Peripheral Nerve Injury.
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生物发光光遗传学：一种促进周围神经损伤后轴突再生的新型实验疗法
DOI：
10.3390/ijms22137217
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发表时间：
2021-07-05
影响因子：
5.6
通讯作者：
Wynans C
中科院分区：
文献类型：
--
作者：
English AW;Berglund K;Carrasco D;Goebel K;Gross RE;Isaacson R;Mistretta OC;Wynans C
周围神经损伤（PNI）后的功能恢复较差，主要是因为受损轴突的再生缓慢且不完全。提高受损轴突兴奋性的实验性疗法在促进再生方面已被证明非常成功，但其临床适用性受到限制。生物发光光遗传学（BL - OG）利用发光视蛋白，即发光的荧光素酶和感光离子通道的融合蛋白，如果暴露于合适的底物，可用于提高神经元兴奋性。兴奋性发光视蛋白在转基因小鼠的运动神经元以及用腺相关病毒载体转导的野生型小鼠中表达。腹腔注射腔肠素（CTZ，一种已知的荧光素酶底物）在外周轴突中产生强烈的生物发光。这种生物发光提高了运动神经元的兴奋性。在坐骨神经切断和修复后立即单次给予CTZ，可显著促进运动轴突再生。损伤后4周，复合肌肉动作电位比对照组大3 - 4倍。转基因小鼠的观察结果与使用病毒载体表达发光视蛋白的小鼠的结果相当。在接受BL - OG治疗的小鼠中，神经损伤4周后成功重新支配肌肉靶点的运动神经元明显多于对照组。生物发光光遗传学是一种有前途的治疗方法，可用于增强周围神经损伤后轴突的再生。
Functional recovery after peripheral nerve injury (PNI) is poor, mainly due to the slow and incomplete regeneration of injured axons. Experimental therapies that increase the excitability of the injured axons have proven remarkably successful in promoting regeneration, but their clinical applicability has been limited. Bioluminescent optogenetics (BL-OG) uses luminopsins, fusion proteins of light-generating luciferase and light-sensing ion channels that could be used to increase neuronal excitability if exposed to a suitable substrate. Excitatory luminopsins were expressed in motoneurons of transgenic mice and in wildtype mice transduced with adeno-associated viral vectors. Intraperitoneal administration of coelenterazine (CTZ), a known luciferase substrate, generated intense bioluminescence in peripheral axons. This bioluminescence increased motoneuron excitability. A single administration of CTZ immediately after sciatic nerve transection and repair markedly enhanced motor axon regeneration. Compound muscle action potentials were 3–4 times larger than controls by 4 weeks after injury. The results observed with transgenic mice were comparable to those of mice in which the luminopsin was expressed using viral vectors. Significantly more motoneurons had successfully reinnervated muscle targets four weeks after nerve injury in BL-OG treated mice than in controls. Bioluminescent optogenetics is a promising therapeutic approach to enhancing axon regeneration after PNI.
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影响因子：
4.2
作者：
Jaiswal PB;Tung JK;Gross RE;English AW
通讯作者：
English AW
DOI：
10.1523/jneurosci.1411-11.2012
发表时间：
2012-04-04
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Wilhelm JC;Xu M;Cucoranu D;Chmielewski S;Holmes T;Lau KS;Bassell GJ;English AW
通讯作者：
English AW
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DOI：
10.1073/pnas.1703601115
发表时间：
2018-01-09
影响因子：
11.1
作者：
Li, Xiangning;Yu, Bin;Qiu, Zilong
通讯作者：
Qiu, Zilong
影响因子：
3.4
作者：
Ward, Patricia J.;Clanton, Scott L., II;English, Arthur W.
通讯作者：
English, Arthur W.
DOI：
10.2106/00004623-196345060-00006
发表时间：
1963-01-01
影响因子：
5.3
作者：
BASMAJIAN, JV;STECKO, G
通讯作者：
STECKO, G