Altered autophagy gene expression and persistent atrophy suggest impaired remodeling in chronic hemiplegic human skeletal muscle

Abstract

Introduction: Upper motor neuron lesions after stroke are a major cause of disability. We aimed to determine whether skeletal muscles from these patients display typical molecular signatures of inflammation, growth arrest, and atrophy.

Methods: Muscle biopsies were analyzed for morphological, histochemical, ultrastructural, and molecular features indicative of changes in gene expression involved in muscle atrophy.

Results: Chronic hemiplegia resulted in ~9.5% atrophy, fiber type shifts, and histochemical and ultrastructural signs of impaired remodeling. TNF and TWEAK expressions were unaltered, but MSTN mRNA was lower (-73%, P < 0.05) in paretic tibialis anterior vs. age-matched controls. The expression of autophagy-related genes (BCN-1, LC3, and GABARAPL1) was lower in paretic tibialis anterior (-81%, -48%, and -60%, respectively, P < 0.01) and soleus (-85%, -54%, and -60% respectively, P < 0.01) compared with old controls.

Conclusions: Persistent atrophy in chronic spastic hemiplegia may be associated with impaired remodeling partly due to altered autophagy gene expression.