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Molecular Mechanisms of Skeletal Muscle Atrophy in Cerebral Ischemic Stroke
Author(s) -
Mohamed Junaith,
Khan Mohammad,
Ferrandi Peter,
Paez Hector,
Pitzer Christopher,
Stephen Alway
Publication year - 2020
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2020.34.s1.08947
Subject(s) - skeletal muscle , atrophy , stroke (engine) , medicine , muscle atrophy , muscle weakness , weakness , cardiology , pathology , anatomy , mechanical engineering , engineering
Stroke is the leading cause of death and the top cause of adult disability in patients world‐wide. Skeletal muscle is the main effector organ accounting for disability in stroke patients due to severe muscle atrophy and related weakness. However, the molecular signaling mechanisms that cause post‐stroke muscle atrophy remains elusive. To determine the mechanisms, we used a preclinical model of stroke in which we induced 60 minutes middle cerebral artery occlusion (MCAO) followed by 3 days reperfusion. We found that stroke caused a significant brain lesion and motor deficit. Stroke induced severe skeletal muscle atrophy in the paretic tibialis anterior muscle compared to the corresponding tibialis anterior muscle of sham mice, as evidenced by reduced muscle mass and FCA (fiber cross‐sectional area). Our transcriptome analysis showed that stroke altered mRNA expression profile in skeletal muscle. Some of the genes associated with catabolic pathways are highly dysregulated in post‐stroke muscle. We also found that stroke dramatically repressed the protein deacetylase Sirtuin1 (SirT1) gene expression and its function in skeletal muscle. Interestingly, restoring SirT1 function in post‐stroke muscle notably reversed muscle atrophy, in part, through regulating the key players of autophagy and ubiquitin proteasomal pathway. Collectively, our data uncovered a potential mechanism that causes cerebral ischemic stroke‐induced muscle atrophy and identified SirT1 as a critical regulator of post‐stroke muscle mass.