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Myelination dictates axonal viscoelasticity.

Ya-Chen Chuang1,2, Ace Alcantara3, Gloria Fabris2

  • 1Department of Mechanical Engineering, University of Washington, Seattle, Washington, USA.

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|March 6, 2023
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Summary

Child brain development involves increasing myelination, which stiffens axons. This study reveals a direct link between myelination and axonal viscoelasticity, crucial for understanding paediatric brain development and injury.

Keywords:
anisotropydorsal root ganglia (DRG)myelinationoligodendrocyte (OL)viscoelasticity

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Area of Science:

  • Neuroscience
  • Biophysics
  • Developmental Biology

Background:

  • Child brain development features significant myelination, altering neural networks and mechanical properties.
  • Mechanical forces influence neuronal growth, differentiation, maturation, and electrical activity.
  • The precise relationship between myelination, axonal structure, and nerve mechanics at the cellular level remains unclear due to imaging resolution limits.

Purpose of the Study:

  • To investigate the direct relationship between axonal viscoelasticity and changes in fibre anisotropy and myelination during development.
  • To quantify the mechanical properties of axons in relation to myelination progression.

Main Methods:

  • Utilized atomic force microscopy (AFM) combined with in situ fluorescent imaging.
  • Employed primary neuron-oligodendrocyte co-cultures for in vitro studies.
  • Quantified myelination using immunofluorescence and measured axonal stiffness via AFM.

Main Results:

  • Axonal stiffness significantly increases with progressive myelination in vitro.
  • A positive correlation was observed between increased myelination over time and increased axonal stiffness (p=0.001).
  • Myelinated axonal segments exhibited significantly higher Young's modulus than unmyelinated segments (p<0.0001), with myelin sheath dominating temporal viscoelasticity regulation.

Conclusions:

  • Established a direct link between myelination, axonal orientation, and viscoelasticity.
  • Provided insights into the mechanical microenvironment of the developing paediatric brain.
  • Findings have implications for understanding developmental brain disorders and paediatric brain injury.