title: Localisation of N-acetylaspartate in oligodendrocytes/myelin.
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.
authors.affiliation: Department of Anatomy, Institute of Basic Medical Sciences, University of Oslo, PO Box 1105, 0317, Oslo, Norway.
authors.forename: Kaja
authors.initials: K
authors.lastname: Nordengen
authors.forename: Christoph
authors.initials: C
authors.lastname: Heuser
authors.forename: Johanne Egge
authors.initials: JE
authors.lastname: Rinholm
authors.forename: Reuben
authors.initials: R
authors.lastname: Matalon
authors.forename: Vidar
authors.initials: V
authors.lastname: Gundersen
mesh_terms: D000818:Animals; D001224:Aspartic Acid / Q000031:analogs & derivatives* / Q000032:analysis / Q000276:immunology; D001369:Axons / Q000737:chemistry; D001921:Brain / Q000648:ultrastructure*; D001923:Brain Chemistry; D066146:Cell Body / Q000737:chemistry; D066128:Gray Matter / Q000737:chemistry; D051379:Mice; D008928:Mitochondria / Q000737:chemistry; D009186:Myelin Sheath / Q000737:chemistry*; D009474:Neurons / Q000737:chemistry; D009836:Oligodendroglia / Q000737:chemistry*; D017208:Rats, Wistar; D066127:White Matter / Q000737:chemistry
chemical_list: D001224:Aspartic Acid; C000179:N-acetylaspartate