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Accumulation of STIM 1 is associated with the degenerative muscle fibre phenotype in ALS and other neurogenic atrophies
Author(s) -
Goswami Anand,
Jesse Christofer Marvin,
Chandrasekar Akila,
Bushuven Eva,
Vollrath Jan Tilmann,
Dreser Alice,
Katona Istvan,
Beyer Cordian,
Johann Sonja,
Feller A. C.,
Grond M.,
Wagner S.,
Nikolin Stefan,
Troost Dirk,
Weis Joachim
Publication year - 2015
Publication title -
neuropathology and applied neurobiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.538
H-Index - 95
eISSN - 1365-2990
pISSN - 0305-1846
DOI - 10.1111/nan.12164
Subject(s) - denervation , amyotrophic lateral sclerosis , atrophy , muscle atrophy , skeletal muscle , neurodegeneration , muscle biopsy , pathology , neuromuscular junction , calcium , myocyte , biology , homeostasis , chemistry , microbiology and biotechnology , anatomy , medicine , biopsy , neuroscience , disease
Aim Upon denervation, skeletal muscle fibres initiate complex changes in gene expression. Many of these genes are involved in muscle fibre remodelling and atrophy. Amyotrophic lateral sclerosis ( ALS ) leads to progressive neurodegeneration and neurogenic muscular atrophy (NMA). Disturbed calcium homeostasis and misfolded protein aggregation both in motor neurones and muscle fibres are key elements of ALS pathogenesis that are mutually interdependent. Therefore, we hypothesized that the calcium sensor STIM 1 might be abnormally modified and involved in muscle fibre degeneration in ALS and other types of NMA . Methods We examined ALS and NMA patient biopsy and autopsy tissue and tissue from G 93 A SOD 1 mice by immunohistochemistry and immunoblotting. Results In normal human and mouse muscle STIM 1 was found to be differentially expressed in muscle fibres of different types and to concentrate at neuromuscular junctions, compatible with its known role in calcium sensing. Denervated muscle fibres of sALS and NMA cases and SOD 1 mice showed diffusely increased STIM 1 immunoreactivity along with ubiquitinated material. In addition, distinct focal accumulations of STIM 1 were observed in target structures within denervated fibres of sALS and other NMA as well as SOD 1 mouse muscles. Large STIM 1‐immunoreactive structures were found in ALS ‐8 patient muscle harbouring the P 56 S mutation in the ER protein VAPB . Conclusion These findings suggest that STIM 1 is involved in several ways in the reaction of muscle fibres to denervation, probably reflecting alterations in calcium homeostasis in denervated muscle fibres.