Age-specific localization of NMDA receptors on oligodendrocytes dictates axon function recovery after ischemia

Research output: Contribution to journalReview articlepeer-review

14 Scopus citations

Abstract

Oligodendrocytes and axons are the main targets of an ischemic white matter injury and the resultant loss of axon function underlies the clinical disability in patients who survive a stroke. The cellular mechanisms of ischemic injury change as a function of age in concordance with age-mediated structural changes in white matter. Shorter periods of injury cause rapid and robust loss of axon function together with widespread oligodendrocyte death. While blockade of NMDA receptors fails to benefit axon function, removal of extracellular Ca2+ during ischemia remarkably promotes axon function recovery in young white matter. However, these same approaches hinder axon function recovery and fail to protect oligodendrocytes in aging white matter. The obligatory GluN1 subunit of the NMDA receptor exhibits an age-specific expression pattern such that in young adult white matter, it is mostly localized on oligodendrocyte cell bodies, while in aging white matter, it is also observed on myelin processes. This age-dependent re-localization and redistribution pattern mimics GluN1 expression observed during development, but in reverse order. During development, GluN1 immunoreactivity traffics from astrocytes at postnatal day 4–11 (P4-11) to myelin processes at P12-18 and to oligodendrocytes cell bodies at P19-21. Although immature axons are more resistant to ischemia, blockade of NMDA receptors during ischemia at P4-11 and P12-18 worsens axon function recovery and fails to benefit axons at P19-21. Thus, age-specific expression patterns of NMDA receptor localization may seem to modulate the plasticity of oligodendrocytes and myelin in response to ischemia as a function of age in white matter. This article is part of the Special Issue entitled ‘Oligodendrocytes in Health and Disease’.

Original languageEnglish (US)
Pages (from-to)626-632
Number of pages7
JournalNeuropharmacology
Volume110
DOIs
StatePublished - Nov 1 2016
Externally publishedYes

Keywords

  • Axon function
  • Ca
  • Compound action potential
  • Development
  • Electrophysiology
  • Myelin
  • Optic nerve

ASJC Scopus subject areas

  • Pharmacology
  • Cellular and Molecular Neuroscience

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