Research Findings

2026.06.10

Scg2 drives corticospinal circuit reorganization with spinal premotor interneurons and astrocytes for motor recovery after stroke in mice.

Nat Commun. 2026 Jun 9;17(1):4880. doi: 10.1038/s41467-026-73518-x.

Sato T1,2, Nakamura Y1,2, Hoshina K1,2, Inoue K3,4, Takada M3,5, Yano M6,7, Matsuzawa H8,9, Ueno M1,2.

  1. Department of System Pathology for Neurological Disorders, Brain Research Institute, Niigata University.
  2. Department of Systems Neuropathology and Neural Repair, Brain Research Institute, Niigata University.
  3. Institute for the Evolutionary Origins of Human Behavior, Kyoto University.
  4. Department of Integrative Anatomy, Graduate School of Medical Sciences and Medical School, Nagoya City University.
  5. Department of Neurology, Graduate School of Medicine, The University of Osaka.
  6. Division of Neurobiology and Anatomy, Graduate School of Medical and Dental Sciences, Niigata University.
  7. Core Research Facilities for Basic Science Research Center for Medical Science, The Jikei University School of Medicine.
  8. Center for Integrated Human Brain Science, Niigata University.
  9. Center for Advanced Medicine and Clinical Research, Sapporo Hakuyokai Hospital.

Abstract

Brain injuries such as stroke damage neural circuitry and lead to functional deficits. Spared motor pathways are often reorganized for recovery; however, the connectivity and mechanisms that drive the reorganization are largely unknown. Here, we demonstrate structural and functional connectivity reformed by corticospinal axons after stroke in male mice and determine a secretory protein that drives the reorganization. We first find that corticospinal axons innervate the denervated cervical cord and reconnect to premotor V2a interneurons after stroke. Kinematic analyses and chemogenetic silencing reveal their contribution to motor recovery. Translated mRNA expression analyses identify a secretory protein secretogranin II (Scg2), which is upregulated in astrocytes by injury-induced ATP and in V2a neurons by rehabilitation-induced neural activity. Scg2 promotes axon growth via cAMP and S6 and enhances axon rewiring, while its knockdown attenuates it. Our data reveal the neural substrate and molecular mechanism to induce reorganization and recovery, providing therapeutic targets for central nervous system (CNS) injuries.

*Reprinted under the CC BY-NC-ND 4.0 license.

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