Calcium Influx Through Plasma-Membrane Nanoruptures Drives Axon Degeneration in a Model of Multiple Sclerosis

Neuron. 2019 Feb 20;101(4):615-624.e5. doi: 10.1016/j.neuron.2018.12.023. Epub 2019 Jan 24.

Abstract

Axon loss determines persistent disability in multiple sclerosis patients. Here, we use in vivo calcium imaging in a multiple sclerosis model to show that cytoplasmic calcium levels determine the choice between axon loss and survival. We rule out the endoplasmic reticulum, glutamate excitotoxicity, and the reversal of the sodium-calcium exchanger as sources of intra-axonal calcium accumulation and instead identify nanoscale ruptures of the axonal plasma membrane as the critical path of calcium entry.

Keywords: axon degeneration; calcium imaging; experimental autoimmune encephalomyelitis; in vivo microscopy; multiple sclerosis; plasma membrane.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Axons / metabolism*
  • Axons / pathology
  • Calcium / metabolism*
  • Cell Membrane / metabolism
  • Cell Membrane / pathology*
  • Female
  • Ion Transport
  • Male
  • Mice
  • Multiple Sclerosis / etiology
  • Multiple Sclerosis / metabolism*

Substances

  • Calcium