Acquired demyelination but not genetic developmental defects in myelination leads to brain tissue stiffness changes

Research output: Contribution to journalResearch articleContributedpeer-review

Contributors

  • Dominic Eberle - , Center for Regenerative Therapies Dresden (Author)
  • Georgia Fodelianaki - , University Hospital Carl Gustav Carus Dresden, Technische Universität Dresden (Author)
  • Thomas Kurth - , Core Facility Electron Microscopy & Histology, Center for Molecular and Cellular Bioengineering (CMCB) (Author)
  • Anna Jagielska - , Massachusetts Institute of Technology (Author)
  • Stephanie Möllmert - , Max Planck Institute for the Science of Light, Technische Universität Dresden (Author)
  • Elke Ulbricht - , Technische Universität Dresden (Author)
  • Katrin Wagner - , Technische Universität Dresden (Author)
  • Anna V. Taubenberger - , Technische Universität Dresden (Author)
  • Nicole Träber - , Technische Universität Dresden, Leibniz Institute of Polymer Research Dresden (Author)
  • Joan Carles Escolano - , Max Planck Institute for the Science of Light, Technische Universität Dresden (Author)
  • Krystyn J. Van Vliet - , Massachusetts Institute of Technology (Author)
  • Jochen Guck - , Max Planck Institute for the Science of Light, Technische Universität Dresden (Author)

Abstract

Changes in axonal myelination are an important hallmark of aging and a number of neurological diseases. Demyelinated axons are impaired in their function and degenerate over time. Oligodendrocytes, the cells responsible for myelination of axons, are sensitive to mechanical properties of their environment. Growing evidence indicates that mechanical properties of demyelinating lesions are different from the healthy state and thus have the potential to affect myelinating potential of oligodendrocytes. We performed a high-resolution spatial mapping of the mechanical heterogeneity of demyelinating lesions using atomic force microscope-enabled indentation. Our results indicate that the stiffness of specific regions of mouse brain tissue is influenced by age and degree of myelination. Here we specifically demonstrate that acquired acute but not genetic demyelination leads to decreased tissue stiffness, which could influence the remyelination potential of oligodendrocytes. We also demonstrate that specific brain regions have unique ranges of stiffness in white and grey matter. Our ex vivo findings may help the design of future in vitro models to mimic the mechanical environment of the brain in healthy and diseased states. The mechanical properties of demyelinating lesions reported here may facilitate novel approaches in treating demyelinating diseases such as multiple sclerosis. Statement of Significance: Mechanical characteristics of a cell's environment can have a profound influence on its biological properties. Neuronal and glial cells are sensitive to mechanical input during development, in disease and regeneration. Sustained tensile strain can promote differentiation of oligodendrocyte progenitor cells into mature oligodendrocytes, which are responsible for the myelination of axons. Changing myelination is an important hallmark in human aging and disease, such as multiple sclerosis. Our hypothesis is that these diseases might be characterized by altered tissue stiffness and that this has an influence on remyelination potential. Here we investigate tissue stiffness profiles of healthy, aged and disease model mice. Manipulating the tissue stiffness might be another promising approach for new treatments.

Details

Original languageEnglish
Article number100019
JournalBrain Multiphysics
Volume1
Publication statusPublished - Nov 2020
Peer-reviewedYes

Keywords

DFG Classification of Subject Areas according to Review Boards

Sustainable Development Goals

Keywords

  • Atomic force microscopy, Cuprizone, Demyelination, Multiple sclerosis, Shiverer, Tissue stiffness