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Localisation of N-acetylaspartate in oligodendrocytes/myelin

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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.

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Acknowledgments

We thank Anna-Bjørg Bore for technical assistance, especially with the Woelcke staining. We thank Sylvia Szucs for help with handling the Canavan mice and the ASPA antibodies. The NAA antibodies were a kind gift from John R. Moffett and Joseph H. Neale (Georgetown University, Washington, US). This work was supported by grants from the Research Council of Norway (grant number 170441/V40).

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Authors and Affiliations

  1. Department of Anatomy, Institute of Basic Medical Sciences, University of Oslo, PO Box 1105, 0317, Oslo, Norway

    Kaja Nordengen, Christoph Heuser, Johanne Egge Rinholm & Vidar Gundersen

  2. Institute of Molecular Medicine and Experimental Immunology, Rheinische Friedrich Wilhelms University, Bonn, Germany

    Christoph Heuser

  3. Janelia Farm Research Campus, Howard Hughes Medical Institute, Ashburn, USA

    Johanne Egge Rinholm

  4. Department of Pediatrics, University of Texas Medical Branch, Galveston, USA

    Reuben Matalon

  5. Department of Neurology, Oslo University Hospital, Rikshospitalet, Oslo, Norway

    Vidar Gundersen

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  1. Kaja Nordengen
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Correspondence to Vidar Gundersen.

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Nordengen, K., Heuser, C., Rinholm, J.E. et al. Localisation of N-acetylaspartate in oligodendrocytes/myelin. Brain Struct Funct 220, 899–917 (2015). https://doi.org/10.1007/s00429-013-0691-7

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