title: Oligodendrocytes Do Not Export NAA-Derived Aspartate In Vitro.
abstract: Oligodendroglial cells are known to de-acetylate the N-acetylaspartate (NAA) synthesized and released by neurons and use it for lipid synthesis. However, the role of NAA regarding their intermediary metabolism remains poorly understood. Two hypotheses were proposed regarding the fate of aspartate after being released by de-acetylation: (1) aspartate is metabolized in the mitochondria of oligodendrocyte lineage cells; (2) aspartate is released to the medium. We report here that aspartoacylase mRNA expression increases when primary rat oligodendrocyte progenitor cells (OPCs) differentiate into mature cells in culture. Moreover, characterising metabolic functions of acetyl coenzyme A and aspartate from NAA catabolism in mature oligodendrocyte cultures after 5 days using isotope-labelled glucose after 5-days of differentiation we found evidence of extensive NAA metabolism. Incubation with [1,6-13C]glucose followed by gas chromatography-mass spectrometry and high performance liquid chromatography analyses of cell extracts and media in the presence and absence of NAA established that the acetate moiety produced by hydrolysis of NAA does not enter mitochondrial metabolism in the form of acetyl coenzyme A. We also resolved the controversy concerning the possible release of aspartate to the medium: aspartate is not released to the medium by oligodendrocytes in amounts detectable by our methods. Therefore we propose that: aspartate released from NAA joins the cytosolic aspartate pool rapidly and takes part in the malate-aspartate shuttle, which transports reducing equivalents from glycolysis into the mitochondria for ATP production and enters the tricarboxylic acid cycle at a slow rate.
authors.affiliation: Wellcome Trust-Medical Research Council Cambridge Stem Cell Institute, Anne McLaren Laboratory and Department of Clinical Neurosciences, University of Cambridge, West Forvie Building, Robinson Way, Cambridge, CB2 0SZ, UK.
authors.forename: Ana
authors.initials: A
authors.lastname: I Amaral
authors.affiliation: Department of Pharmacy, College of Health Sciences, Mekelle University, Tigray, Ethiopia.
authors.forename: Mussie Ghezu
authors.initials: MG
authors.lastname: Hadera
authors.affiliation: Wellcome Trust-Medical Research Council Cambridge Stem Cell Institute, Anne McLaren Laboratory and Department of Clinical Neurosciences, University of Cambridge, West Forvie Building, Robinson Way, Cambridge, CB2 0SZ, UK. mrk25@cam.ac.uk.
authors.forename: Mark
authors.initials: M
authors.lastname: Kotter
authors.affiliation: Department of Neuroscience, Faculty of Medicine, Norwegian University of Science and Technology (NTNU), PO Box 8905, MTFS, 7491, Trondheim, Norway. Ursula.sonnewald@ntnu.no.|Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, 2100, Denmark. Ursula.sonnewald@ntnu.no.
authors.forename: Ursula
authors.identifier: http://orcid.org/0000-0001-5940-6927
authors.initials: U
authors.lastname: Sonnewald
mesh_terms: D000105:Acetyl Coenzyme A / Q000378:metabolism; D000107:Acetylation; D000818:Animals; D000831:Animals, Newborn; D001224:Aspartic Acid / Q000031:analogs & derivatives* / Q000378:metabolism; D002478:Cells, Cultured; D005947:Glucose / Q000378:metabolism; D006868:Hydrolysis; D019344:Lactic Acid / Q000378:metabolism; D008928:Mitochondria / Q000378:metabolism; D009836:Oligodendroglia / Q000378:metabolism*; D061251:Primary Cell Culture; D016548:Prosencephalon / Q000166:cytology / Q000378:metabolism; D017207:Rats, Sprague-Dawley
chemical_list: D001224:Aspartic Acid; D019344:Lactic Acid; D000105:Acetyl Coenzyme A; C000179:N-acetylaspartate; D005947:Glucose
keywords: Acetate; Aspartate; Brain cells; Energy metabolism; Glia; Glucose