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

• 成果类型: Article
• 署名作者: Squair, Jordan W.; Milano, Marco; de Coucy, Alexandra; Gautier, Matthieu; Skinnider, Michael A.; James, Nicholas D.; Cho, Newton; Lasne, Anna; Kathe, Claudia; Hutson, Thomas H.; Ceto, Steven; Baud, Laetitia; Galan, Katia; Aureli, Viviana; Laskaratos, Achilleas; Barraud, Quentin; Deming, Timothy J.; Kohman, Richie E.; Schneider, Bernard L.; He, Zhigang; Bloch, Jocelyne; Sofroniew, Michael V.; Courtine, Gregoire; Anderson, Mark A.
• 署名单位: Swiss School of Public Health (SSPH+); Swiss Federal Institutes of Technology Domain; Ecole Polytechnique Federale de Lausanne; University of Lausanne; Centre Hospitalier Universitaire Vaudois (CHUV); University of Lausanne; University of Lausanne; Centre Hospitalier Universitaire Vaudois (CHUV); Swiss Federal Institutes of Technology Domain; Ecole Polytechnique Federale de Lausanne; University of Lausanne; Centre Hospitalier Universitaire Vaudois (CHUV); University of California System; University of California Los Angeles; University of California System; University of California Los Angeles; Swiss Federal Institutes of Technology Domain; Ecole Polytechnique Federale de Lausanne; Swiss School of Public Health (SSPH+); Swiss Federal Institutes of Technology Domain; Ecole Polytechnique Federale de Lausanne; Harvard University; Harvard University Medical Affiliates; Boston Children's Hospital; Harvard Medical School; University of California System; University of California Los Angeles; University of California Los Angeles Medical Center; David Geffen School of Medicine at UCLA
• 刊物名称: SCIENCE
• ISSN/ISSBN: 0036-12919
• DOI: 10.1126/science.adi6412
• 发表日期: 2023-09-22
• 页码: 1338-1345
• 关键词: central-nervous-system; spinal-cord; brain-stem; circuit reorganization; axonal regeneration; synapse formation; GROWTH; motor; ORGANIZATION; cells

摘要

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.