Functional ionotropic glutamate receptors on peripheral axons and myelin

Muscle Nerve. 2016 Sep;54(3):451-9. doi: 10.1002/mus.25078. Epub 2016 Jul 4.

Abstract

Introduction: Neurotransmitter-dependent signaling is traditionally restricted to axon terminals. However, receptors are present on myelinating glia, suggesting that chemical transmission may also occur along axons.

Methods: Confocal microscopy and Ca(2+) -imaging using an axonally expressed FRET-based reporter was used to measure Ca(2+) changes and morphological alterations in myelin in response to stimulation of glutamate receptors.

Results: Activation of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) or N-methyl-D-aspartate (NMDA) receptors induced a Ca(2+) increase in axon cylinders. However, only the latter caused structural alterations in axons, despite similar Ca(2+) increases. Myelin morphology was significantly altered by NMDA receptor activation, but not by AMPA receptors. Cu(2+) ions influenced the NMDA receptor-dependent response, suggesting that this metal modulates axonal receptors. Glutamate increased ribosomal signal in Schwann cell cytoplasm.

Conclusions: Axon cylinders and myelin of peripheral nervous system axons respond to glutamate, with a consequence being an increase in Schwann cell ribosomes. This may have implications for nerve pathology and regeneration. Muscle Nerve 54: 451-459, 2016.

Keywords: AMPA; Ca2+ imaging; axon; confocal microscopy; copper NMDA; myelin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Axons / metabolism*
  • Bacterial Proteins / genetics
  • Bacterial Proteins / metabolism
  • Calcium / metabolism
  • Copper / metabolism
  • Female
  • Fluorescence Resonance Energy Transfer
  • Luminescent Proteins / genetics
  • Luminescent Proteins / metabolism
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Microscopy, Confocal
  • Myelin Sheath / metabolism*
  • Receptors, Ionotropic Glutamate / genetics
  • Receptors, Ionotropic Glutamate / metabolism*
  • Statistics, Nonparametric

Substances

  • Bacterial Proteins
  • Luminescent Proteins
  • Receptors, Ionotropic Glutamate
  • yellow fluorescent protein, Bacteria
  • Copper
  • Calcium

Grants and funding