Recovery of walking after paralysis by regenerating characterized neurons to their natural target region-Reference-Cited by-同舟云学术

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

Published:2023-09-22 Issue:6664 Volume:381 Page:1338-1345
ISSN:0036-8075
Container-title:Science
language:en
Short-container-title:Science

Author:

Squair Jordan W.¹²³^ORCID,Milano Marco¹³^ORCID,de Coucy Alexandra¹³^ORCID,Gautier Matthieu¹³^ORCID,Skinnider Michael A.¹³^ORCID,James Nicholas D.¹³^ORCID,Cho Newton¹³^ORCID,Lasne Anna¹³,Kathe Claudia¹³^ORCID,Hutson Thomas H.¹³⁴^ORCID,Ceto Steven¹³^ORCID,Baud Laetitia¹³^ORCID,Galan Katia¹³^ORCID,Aureli Viviana¹²³⁵^ORCID,Laskaratos Achilleas³⁵^ORCID,Barraud Quentin¹³^ORCID,Deming Timothy J.⁶^ORCID,Kohman Richie E.⁴^ORCID,Schneider Bernard L.¹⁷⁸^ORCID,He Zhigang⁹^ORCID,Bloch Jocelyne¹²³⁵^ORCID,Sofroniew Michael V.¹⁰^ORCID,Courtine Gregoire¹²³⁵^ORCID,Anderson Mark A.¹³⁴⁵^ORCID

Affiliation:

1. NeuroX Institute, School of Life Sciences, Swiss Federal Institute of Technology (EPFL), 1015 Lausanne, Switzerland.

2. Department of Neurosurgery, Lausanne University Hospital (CHUV) and University of Lausanne (UNIL), 1005 Lausanne, Switzerland.

3. Defitech Center for Interventional Neurotherapies (NeuroRestore), CHUV/UNIL/EPFL, 1005 Lausanne, Switzerland.

4. Wyss Center for Bio and Neuroengineering, 1202 Geneva, Switzerland.

5. Department of Clinical Neuroscience, Lausanne University Hospital (CHUV) and University of Lausanne (UNIL), 1005 Lausanne, Switzerland.

6. Departments of Bioengineering, Chemistry and Biochemistry, University of California, Los Angeles, Los Angeles, CA 90095, USA.

7. Bertarelli Platform for Gene Therapy, Swiss Federal Institute of Technology (EPFL), 1015 Lausanne, Switzerland.

8. Brain Mind Institute, School of Life Sciences, Swiss Federal Institute of Technology (EPFL), 1015 Lausanne, Switzerland.

9. F.M. Kirby Neurobiology Center, Department of Neurology, Boston Children's Hospital, Harvard Medical School, Boston, MA 02115, USA.

10. Department of Neurobiology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.

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.

Publisher

American Association for the Advancement of Science (AAAS)

Subject

Multidisciplinary

Link

https://www.science.org/doi/pdf/10.1126/science.adi6412

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