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

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.