Your browser doesn't support javascript.
loading
Lesion level-dependent systemic muscle wasting after spinal cord injury is mediated by glucocorticoid signaling in mice.
Harrigan, Markus E; Filous, Angela R; Vadala, Christopher P; Webb, Amy; Pietrzak, Maciej; Sahenk, Zarife; Prüss, Harald; Reiser, Peter J; Popovich, Phillip G; Arnold, W David; Schwab, Jan M.
Afiliación
  • Harrigan ME; Department of Neurology, Spinal Cord Injury Division (Paraplegiology), College of Medicine, Ohio State University, Wexner Medical Center, Columbus, OH 43210, USA.
  • Filous AR; Medical Scientist Training Program, College of Medicine, Ohio State University, Wexner Medical Center, Columbus, OH 43210, USA.
  • Vadala CP; Neuroscience Research Institute, Ohio State University, Columbus, OH 43210, USA.
  • Webb A; Belford Center for Spinal Cord Injury, Ohio State University, Wexner Medical Center, Columbus, OH 43210, USA.
  • Pietrzak M; Department of Neurology, Spinal Cord Injury Division (Paraplegiology), College of Medicine, Ohio State University, Wexner Medical Center, Columbus, OH 43210, USA.
  • Sahenk Z; Neuroscience Research Institute, Ohio State University, Columbus, OH 43210, USA.
  • Prüss H; Belford Center for Spinal Cord Injury, Ohio State University, Wexner Medical Center, Columbus, OH 43210, USA.
  • Reiser PJ; Department of Neurology, Spinal Cord Injury Division (Paraplegiology), College of Medicine, Ohio State University, Wexner Medical Center, Columbus, OH 43210, USA.
  • Popovich PG; Neuroscience Research Institute, Ohio State University, Columbus, OH 43210, USA.
  • Arnold WD; Belford Center for Spinal Cord Injury, Ohio State University, Wexner Medical Center, Columbus, OH 43210, USA.
  • Schwab JM; Department of Biomedical Informatics, College of Medicine, Ohio State University, Wexner Medical Center, Columbus, OH 43210, USA.
Sci Transl Med ; 15(727): eadh2156, 2023 12 20.
Article en En | MEDLINE | ID: mdl-38117902
ABSTRACT
An incomplete mechanistic understanding of skeletal muscle wasting early after spinal cord injury (SCI) precludes targeted molecular interventions. Here, we demonstrated systemic wasting that also affected innervated nonparalyzed (supralesional) muscles and emerged within 1 week after experimental SCI in mice. Systemic muscle wasting caused muscle weakness, affected fast type 2 myofibers preferentially, and became exacerbated after high (T3) compared with low (T9) thoracic paraplegia, indicating lesion level-dependent ("neurogenic") mechanisms. The wasting of nonparalyzed muscle and its rapid onset and severity beyond what can be explained by disuse implied unknown systemic drivers. Muscle transcriptome and biochemical analysis revealed a glucocorticoid-mediated catabolic signature early after T3 SCI. SCI-induced systemic muscle wasting was mitigated by (i) endogenous glucocorticoid ablation (adrenalectomy) and (ii) pharmacological glucocorticoid receptor (GR) blockade and was (iii) completely prevented after T3 relative to T9 SCI by genetic muscle-specific GR deletion. These results suggest that neurogenic hypercortisolism contributes to a rapid systemic and functionally relevant muscle wasting syndrome early after paraplegic SCI in mice.
Asunto(s)
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Traumatismos de la Médula Espinal / Glucocorticoides Límite: Animals Idioma: En Revista: Sci Transl Med Asunto de la revista: CIENCIA / MEDICINA Año: 2023 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Traumatismos de la Médula Espinal / Glucocorticoides Límite: Animals Idioma: En Revista: Sci Transl Med Asunto de la revista: CIENCIA / MEDICINA Año: 2023 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos