Scg2 drives reorganization of the corticospinal circuit with spinal premotor interneurons to recover motor function after stroke

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Publicado en:bioRxiv (Jan 22, 2025)
Autor principal: Sato, Tokiharu
Otros Autores: Nakamura, Yuka, Hoshina, Kana, Inoue, Ken-Ichi, Takada, Masahiko, Yano, Masato, Matsuzawa, Hitoshi, Ueno, Masaki
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Cold Spring Harbor Laboratory Press
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Acceso en línea:Citation/Abstract
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LEADER 00000nab a2200000uu 4500
001 3158241900
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022 |a 2692-8205 
024 7 |a 10.1101/2025.01.21.634186  |2 doi 
035 |a 3158241900 
045 0 |b d20250122 
100 1 |a Sato, Tokiharu 
245 1 |a Scg2 drives reorganization of the corticospinal circuit with spinal premotor interneurons to recover motor function after stroke 
260 |b Cold Spring Harbor Laboratory Press  |c Jan 22, 2025 
513 |a Working Paper 
520 3 |a Brain injuries such as stroke damage neural circuitry and lead to functional deficits. Spared motor pathways are often reorganized and contribute to functional recovery; however, the connectivity and molecular mechanisms that drive the reorganization are largely unknown. Here, we demonstrate structural and functional connectivity reformed by spared corticospinal axons after stroke and determine a key secretory protein that drives the reorganization. We first found that corticospinal axons innervate specific areas of the denervated cervical cord after stroke. Anatomical and photometric analyses reveal that the axons reconnect to premotor V2a interneurons. Kinematic analyses of forelimb movements and chemogenetic silencing reveal their contribution to motor recovery. Translated mRNA expression analyses of V2a interneurons and astrocytes in the denervated cervical cord reveal diverse transcripts upregulated in the rewiring process. In particular, a secretory protein Scg2 is upregulated by injury-induced purinergic ATP signals and rehabilitative training-induced neural activity and possesses an ability to promote axon growth via cAMP and S6 signaling. Scg2 overexpression in the denervated cervical cord enhances axon rewiring, while the Scg2 knockdown attenuates it. The present data reveal the neural substrate and molecular mechanism essential to induce reorganization and recovery of the motor system, providing fundamental therapeutic targets for CNS injuries.Competing Interest StatementThe authors have declared no competing interest. 
653 |a Astrocytes 
653 |a Molecular modelling 
653 |a Brain injury 
653 |a Gene expression 
653 |a Structure-function relationships 
653 |a Recovery of function 
653 |a Interneurons 
653 |a Therapeutic targets 
653 |a Neural networks 
653 |a Injuries 
653 |a Stroke 
700 1 |a Nakamura, Yuka 
700 1 |a Hoshina, Kana 
700 1 |a Inoue, Ken-Ichi 
700 1 |a Takada, Masahiko 
700 1 |a Yano, Masato 
700 1 |a Matsuzawa, Hitoshi 
700 1 |a Ueno, Masaki 
773 0 |t bioRxiv  |g (Jan 22, 2025) 
786 0 |d ProQuest  |t Biological Science Database 
856 4 1 |3 Citation/Abstract  |u https://www.proquest.com/docview/3158241900/abstract/embedded/7BTGNMKEMPT1V9Z2?source=fedsrch 
856 4 0 |3 Full Text - PDF  |u https://www.proquest.com/docview/3158241900/fulltextPDF/embedded/7BTGNMKEMPT1V9Z2?source=fedsrch 
856 4 0 |3 Full text outside of ProQuest  |u https://www.biorxiv.org/content/10.1101/2025.01.21.634186v1