Localisation of N-acetylaspartate in oligodendrocytes/myelin

Kaja Nordengen, Christoph Heuser, Johanne Egge Rinholm, Reuben Matalon, Vidar Gundersen

Research output: Contribution to journalArticle

35 Scopus citations

Abstract

The role of N-acetylaspartate in the brain is unclear. Here we used specific antibodies against N-acetylaspartate and immunocytochemistry of carbodiimide-fixed adult rodent brain to show that, besides staining of neuronal cell bodies in the grey matter, N-acetylaspartate labelling was present in oligodendrocytes/myelin in white matter tracts. Immunoelectron microscopy of the rat hippocampus showed that N-acetylaspartate was concentrated in the myelin. Also neuronal cell bodies and axons contained significant amounts of N-acetylaspartate, while synaptic elements and astrocytes were low in N-acetylaspartate. Mitochondria in axons and neuronal cell bodies contained higher levels of N-acetylaspartate compared to the cytosol, compatible with synthesis of N-acetylaspartate in mitochondria. In aspartoacylase knockout mice, in which catabolism of N-acetylaspartate is blocked, the levels of N-acetylaspartate were largely increased in oligodendrocytes/myelin. In these mice, the highest myelin concentration of N-acetylaspartate was found in the cerebellum, a region showing overt dysmyelination. In organotypic cortical slice cultures there was no evidence for N-acetylaspartate-induced myelin toxicity, supporting the notion that myelin damage is induced by the lack of N-acetylaspartate for lipid production. Our findings also implicate that N-acetylaspartate signals on magnetic resonance spectroscopy reflect not only vital neurons but also vital oligodendrocytes/myelin.

Original languageEnglish (US)
Pages (from-to)899-917
Number of pages19
JournalBrain Structure and Function
Volume220
Issue number2
DOIs
StatePublished - Jan 1 2015

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Keywords

  • Aspartate
  • Canavan disease
  • Cerebellum
  • Glutamate
  • Immunogold
  • leukodystrophy

ASJC Scopus subject areas

  • Anatomy
  • Neuroscience(all)
  • Histology

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