Abnormalities of satellite cells function in amyotrophic lateral sclerosis

Abstract

Amyotrophic lateral sclerosis (ALS) is characterized by progressive denervation leading to muscle atrophy prevented, during the early phase, by compensatory reinnervation. Little is known about muscle fibre regeneration capacity in ALS. We have carried out in vivo and in vitro investigation of skeletal muscle in ALS. Seven ALS patients underwent a deltoid muscle biopsy. Immunohistochemical analysis revealed various degrees of denervation- and reinnervation-related changes in the ALS muscle biopsies including satellite cells (SCs) activation and regenerating fibres. Only 3/7 primary cultures of ALS muscle cells were successfully established and had sufficient myogenicity, as assessed by desmin positivity, to be used without further purification. This was in contrast with the cultures derived from control muscles, predominantly desmin-positive cells. Although capable to proliferate in vitro, ALS-derived SCs presented an abnormal senescent-like morphology. Markers of senescence, including senescent-associated (SA)-βGal activity and p16 expression, were increased. Furthermore, ALS-derived SCs were also unable to fully differentiate in vitro as shown by abnormal myotubes morphology and reduced MHC isoform expression, compared to control myotubes. Our study suggests that SC function is altered in ALS. This could limit the efficacy of compensatory processes and therefore could contribute to the progression of muscle atrophy and weakness.

Key words::

• ALS
• muscle
• satellite cells

Acknowledgements

The authors thank Kamel Mamchaoui and Onnik Agbulut, and also Luc Dupuis for helpful and critical reading of the manuscript.

Aude Barani was a recipient of a post-doctoral fellowship form the Association Française contre les Myopathies (AFM) and from the Association for Research in ALS (ARSla). This work was funded by a grant from the European Commission MYOAGE Network, AFM, ANR In-A-Fib, INSERM, CNRS and Université Pierre et Marie Curie.

Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.