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Abstract #0924

Neurochemical signature of the metabolic mechanisms underlying de- & re-myelination in the mouse’s cerebellum

Georges Hankov1,2,3,4, Aline Seuwen1,3, Giovanna D. Ielacqua1,3, Anna E. Mechling2, Eva Mracsko2, Andreas Bruns2, Basil Künnecke2, Markus von Kienlin2, Markus Rudin1,3,4, and Thomas Mueggler2

1Institute for Biomedical Engineering, ETH and University of Zurich, Zurich, Switzerland, 2NORD Discovery & Translational Area, Pharmaceutical research and Early Development, Roche Innovation Center Basel, F. Hoffmann-La Roche Ltd, Basel, Switzerland, 3Institute of Pharmacology and Toxicology, University of Zurich, Zurich, Switzerland, 4Neuroscience Center Zurich, Zurich, Switzerland

Because of an increasing therapeutic need to understand the underlying mechanism of myelin damage and repair in pathologies such as multiple sclerosis (MS), we used 1H-MRS to longitudinally characterize the metabolic changes in the cerebellum associated with de- and re-myelination in the cuprizone mouse model. Our results, in line with similar findings in the corpus callosum, suggest that a group of metabolites provide a unique neurochemical signature of cuprizone induced de- and re-myelination. Additionally, we observe a reversible and robust increase of GABA levels upon cuprizone feeding that goes in contradiction with current trends in clinical studies of MS patients.

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