Journal Article

DZNE-2024-00022

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Lesion level-dependent systemic muscle wasting after spinal cord injury is mediated by glucocorticoid signaling in mice.

Harrigan, M. E. ; Filous, A. R. ; Vadala, C. P. ; Webb, A. ; Pietrzak, M. ; Sahenk, Z. ; Prüss, H.DZNE* ; Reiser, P. J. ; Popovich, P. G. ; Arnold, W. D. ; Schwab, J. M.

2023
AAAS Washington, DC

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Please use a persistent id in citations: doi:10.1126/scitranslmed.adh2156

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.

Keyword(s): Mice (MeSH) ; Animals (MeSH) ; Glucocorticoids (MeSH) ; Spinal Cord Injuries: pathology (MeSH) ; Muscle, Skeletal: metabolism (MeSH) ; Spinal Cord: metabolism (MeSH) ; Glucocorticoids

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Contributing Institute(s):

1. Autoimmune Encephalopathies (AG Prüß)

Research Program(s):

1. 353 - Clinical and Health Care Research (POF4-353) (POF4-353)

Appears in the scientific report 2023

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Database coverage:
; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Essential Science Indicators ; IF >= 15 ; JCR ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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