Recovery of walking after paralysis by regenerating characterized neurons to their natural target region

IF 45.8 1区综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES

Science Pub Date : 2023-09-21 DOI:10.1126/science.adi6412

Jordan W. Squair, Marco Milano, Alexandra de Coucy, Matthieu Gautier, Michael A. Skinnider, Nicholas D. James, Newton Cho, Anna Lasne, Claudia Kathe, Thomas H. Hutson, Steven Ceto, Laetitia Baud, Katia Galan, Viviana Aureli, Achilleas Laskaratos, Quentin Barraud, Timothy J. Deming, Richie E. Kohman, Bernard L. Schneider, Zhigang He, Jocelyne Bloch, Michael V. Sofroniew, Gregoire Courtine, Mark A. Anderson

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引用次数: 0

Abstract

Axon regeneration can be induced across anatomically complete spinal cord injury (SCI), but robust functional restoration has been elusive. Whether restoring neurological functions requires directed regeneration of axons from specific neuronal subpopulations to their natural target regions remains unclear. To address this question, we applied projection-specific and comparative single-nucleus RNA sequencing to identify neuronal subpopulations that restore walking after incomplete SCI. We show that chemoattracting and guiding the transected axons of these neurons to their natural target region led to substantial recovery of walking after complete SCI in mice, whereas regeneration of axons simply across the lesion had no effect. Thus, reestablishing the natural projections of characterized neurons forms an essential part of axon regeneration strategies aimed at restoring lost neurological functions.

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通过将特征神经元再生到其自然目标区域来恢复瘫痪后的行走。

轴突再生可以在解剖学上完全性脊髓损伤（SCI）中诱导，但强大的功能恢复一直难以实现。恢复神经功能是否需要将轴突从特定的神经元亚群定向再生到其天然靶区尚不清楚。为了解决这个问题，我们应用投射特异性和比较性单核RNA测序来鉴定不完全SCI后恢复行走的神经元亚群。我们发现，化学吸引和引导这些神经元的横切轴突到达其自然靶区，可以使小鼠在完全SCI后行走基本恢复，而仅仅穿过损伤的轴突再生没有影响。因此，重建特征神经元的自然投射是轴突再生策略的重要组成部分，旨在恢复失去的神经功能。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Science 综合性期刊-综合性期刊

CiteScore

61.10

自引率

0.90%

发文量

审稿时长

2.1 months

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