gms | German Medical Science

60. Jahrestagung der Deutschen Gesellschaft für Neuropathologie und Neuroanatomie (DGNN)

Deutsche Gesellschaft für Neuropathologie und Neuroanatomie

26. - 28.08.2015, Berlin

Accumulation of STIM1 is associated with the degenerative muscle fibre phenotype in ALS and other neurogenic atrophies

Meeting Abstract

  • corresponding author presenting/speaker Christopher Marvin Jesse - RWTH Aachen University and JARA Brain Translational Medicine, Institute of Neuropathology, Aachen, Germany
  • Anand Goswami - RWTH Aachen University and JARA Brain Translational Medicine, Institute of Neuropathology, Aachen, Germany
  • Akila Chandrasekar - RWTH Aachen University and JARA Brain Translational Medicine, Institute of Neuropathology, Aachen, Germany
  • Eva Bushuven - RWTH Aachen University and JARA Brain Translational Medicine, Institute of Neuropathology, Aachen, Germany
  • Jan Tilmann Vollrath - RWTH Aachen University and JARA Brain Translational Medicine, Institute of Neuropathology, Aachen, Germany
  • Alice Dreser - RWTH Aachen University and JARA Brain Translational Medicine, Institute of Neuropathology, Aachen, Germany
  • Istvan Katona - RWTH Aachen University and JARA Brain Translational Medicine, Institute of Neuropathology, Aachen, Germany
  • Cordian Beyer - RWTH Aachen University, Institute of Neuroanatomy, Aachen, Germany
  • Sonja Johann - RWTH Aachen University, Institute of Neuroanatomy, Aachen, Germany
  • Alfred C. Feller - University Hospital Schleswig-Holstein, Institute of Pathology, Luebeck, Germany
  • Martin Grond - District Hospital Siegen, Department of Neurology, Siegen, Germany
  • S. Wagner - District Hospital Siegen, Department of Neurology, Siegen, Germany
  • Stefan Nikolin - RWTH Aachen University and JARA Brain Translational Medicine, Institute of Neuropathology, Aachen, Germany
  • Dirk Troost - Academic Medical Centre, Division of Neuropathology, Department of Pathology, Amsterdam, Netherlands
  • Joachim Weis - RWTH Aachen University and JARA Brain Translational Medicine, Institute of Neuropathology, Aachen, Germany

Deutsche Gesellschaft für Neuropathologie und Neuroanatomie. 60th Annual Meeting of the German Society for Neuropathology and Neuroanatomy (DGNN). Berlin, 26.-28.08.2015. Düsseldorf: German Medical Science GMS Publishing House; 2015. Doc15dgnnP7

doi: 10.3205/15dgnn31, urn:nbn:de:0183-15dgnn313

Veröffentlicht: 25. August 2015

© 2015 Jesse et al.
Dieser Artikel ist ein Open-Access-Artikel und steht unter den Lizenzbedingungen der Creative Commons Attribution 4.0 License (Namensnennung). Lizenz-Angaben siehe http://creativecommons.org/licenses/by/4.0/.


Gliederung

Text

Questions: 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 STIM1 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 G93A SOD1 mice by immunohistochemistry and immunoblotting.

Results: In normal human and mouse muscle STIM1 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 SOD1 mice showed diffusely increased STIM1 immunoreactivity along with ubiquitinated material. In addition, distinct focal accumulations of STIM1 were observed in target structures within denervated fibres of sALS and other NMA as well as SOD1 mouse muscles. Large STIM1-immunoreactive structures were found in ALS-8 patient muscle harbouring the P56S mutation in the ER protein VAPB.

Conclusions: These findings suggest that STIM1 is involved in several ways in the reaction of muscle fibres to denervation, probably reflecting alterations in calcium homeostasis in denervated muscle fibres.