Transcriptomics reveals transient and dynamic muscle fibrosis and atrophy differences following spinal cord injury in rats

Autor: Hui Jean Kok, Drew B. Fletcher, Jacob C. Oster, Christine F. Conover, Elisabeth R. Barton, Joshua F. Yarrow
Jazyk: angličtina
Rok vydání: 2024
Předmět:
Zdroj: Journal of Cachexia, Sarcopenia and Muscle, Vol 15, Iss 4, Pp 1309-1323 (2024)
Druh dokumentu: article
ISSN: 2190-6009
2190-5991
DOI: 10.1002/jcsm.13476
Popis: Abstract Background The rate and magnitude of skeletal muscle wasting after severe spinal cord injury (SCI) exceeds most other disuse conditions. Assessing the time course of molecular changes can provide insight into the progression of muscle wasting post‐SCI. The goals of this study were (1) to identify potential targets that may prevent the pathologic features of SCI in soleus muscles and (2) to establish therapeutic windows for treating these pathologic changes. Methods Four‐month‐old Sprague–Dawley male rats received T9 laminectomy (SHAM surgery) or severe contusion SCI. Hindlimb locomotor function was assessed weekly, with soleus muscles obtained 1 week, 2 weeks, 1 month and 3 months post‐surgery (n = 6–7 per group per timepoint). RNA was extracted from muscles for bulk RNA‐sequencing analysis (n = 3–5 per group per timepoint). Differentially expressed genes (DEGs) were evaluated between age‐matched SHAM and SCI animals. Myofiber size, muscle fibre type and fibrosis were assessed on contralateral muscles. Results SCI produced immediate and persistent hindlimb paralysis, with Basso–Beattie–Bresnahan locomotor scores remaining below 7 throughout the study, contributing to a progressive 25–50% lower soleus mass and myofiber atrophy versus SHAM (P 50% higher ECM areas and hydroxyproline levels in SCI muscles (P
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