Mass spectrometry-based proteomic characterization of the middle-aged mouse brain for animal model research of neuromuscular diseases


Submitted: 29 June 2023
Accepted: 28 July 2023
Published: 3 August 2023
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Authors

  • Paul Dowling Department of Biology, Maynooth University, National University of Ireland, Maynooth, Co. Kildare, Ireland; Kathleen Lonsdale Institute for Human Health Research, Maynooth University, Maynooth, Co. Kildare, Ireland. https://orcid.org/0000-0002-9290-9267
  • Margit Zweyer Department of Neonatology and Paediatric Intensive Care, Children’s Hospital, University of Bonn, Bonn, Germany; German Centre for Neurodegenerative Diseases, University of Bonn, Bonn, Germany.
  • Hemmen Sabir Department of Neonatology and Paediatric Intensive Care, Children’s Hospital, University of Bonn, Bonn, Germany; German Centre for Neurodegenerative Diseases, University of Bonn, Bonn, Germany. https://orcid.org/0000-0002-4225-3554
  • Michael Henry National Institute for Cellular Biotechnology, Dublin City University, Dublin, Ireland. https://orcid.org/0000-0001-5312-4961
  • Paula Meleady National Institute for Cellular Biotechnology, Dublin City University, Dublin, Ireland. https://orcid.org/0000-0001-5306-310X
  • Dieter Swandulla Institute of Physiology, Medical Faculty, University of Bonn, Bonn, Germany.
  • Kay Ohlendieck Department of Biology, Maynooth University, National University of Ireland, Maynooth, Co. Kildare, Ireland; Kathleen Lonsdale Institute for Human Health Research, Maynooth University, Maynooth, Co. Kildare, Ireland. https://orcid.org/0000-0002-6266-4510

Neuromuscular diseases with primary muscle wasting symptoms may also display multi-systemic changes in the body and exhibit secondary pathophysiological alterations in various non-muscle tissues. In some cases, this includes proteome-wide alterations and/or adaptations in the central nervous system. Thus, in order to provide an improved bioanalytical basis for the comprehensive evaluation of animal models that are routinely used in muscle research, this report describes the mass spectrometry-based proteomic characterization of the mouse brain. Crude tissue extracts were examined by bottom-up proteomics and detected 4558 distinct protein species. The detailed analysis of the brain proteome revealed the presence of abundant cellular proteoforms in the neuronal cytoskeleton, as well as various brain region enriched proteins, including markers of the cerebral cortex, cerebellum, hippocampus and the olfactory bulb. Neuroproteomic markers of specific cell types in the brain were identified in association with various types of neurons and glia cells. Markers of subcellular structures were established for the plasmalemma, nucleus, endoplasmic reticulum, mitochondria and other crucial organelles, as well as synaptic components that are involved in presynaptic vesicle docking, neurotransmitter release and synapse remodelling.


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Dowling, P., Zweyer, M., Sabir, H., Henry, M., Meleady, P., Swandulla, D., & Ohlendieck, K. (2023). Mass spectrometry-based proteomic characterization of the middle-aged mouse brain for animal model research of neuromuscular diseases. European Journal of Translational Myology, 33(3). https://doi.org/10.4081/ejtm.2023.11553

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