Oligodendrocytopathy and astrocytopathy precede myelin loss and blood-brain barrier disruption in a mouse model of osmotic demyelination syndrome

Event Abstract Back to Event Oligodendrocytopathy and astrocytopathy precede myelin loss and blood-brain barrier disruption in a mouse model of osmotic demyelination syndrome Joanna Bouchat1*, Bruno Couturier2, 3, Fabrice Gankam Kengne2, 3, Luc Poncelet4, Jean-Pierre Brion3, Jacques Gilloteaux1 and Charles Nicaise1 1 UNamur, Laboratory of Neurodegenerescence and Regeneration, URPhyM - NARILIS, Belgium 2 Univeristé Libre de Bruxelles, Department of General Internal Medicine, Belgium 3 Université Libre de Bruxelles, Laboratory of Histology, Histopathology and Neuroanatomy, Belgium 4 Université Libre de Bruxelles, Laboratory of Anatomy, Biomechanics and Organogenesis, Belgium Osmotic demyelination syndrome (ODS) is a non-inflammatory disorder of the CNS myelin that occurs following too rapid correction of chronic hyponatremia. The physiopathology remains unclear although hypothetical mechanisms include blood-borne myelinotoxic factors or deleterious osmotic fluctuations focally in white and gray matter-mixed rich regions. To morphologically and functionally investigate the development of ODS in vivo, we generated a novel murine model of ODS. Eriochrome and anti-MBP stainings revealed typical demyelinating lesions in the thalamus, mesencephalon, pons and subcortical regions at 48 hours post-correction in ODS mice brains. Lesions were associated with a significant decrease of APC+ and Cx47+ oligodendrocytes, starting as soon as 24 hours post-correction. Oligodendrocytopathy was temporally and spatially correlated with the loss of astrocyte markers (ALDH1L1, AQP4, S100.) and both with the areas affected by demyelination. Using IgG immunostaining and Evans Blue extravasation assay, we demonstrated that blood-brain barrier disruption started at 48 hours post-correction. Following osmotic insult, Iba1+ microglial cells infiltrated the brain tissue within 12 hours post-correction, while acquiring an activated morphology, from quiescent type A to types B, C and D at latter time points. IL-1ß and LIF mRNA, known to influence myelin integrity, were both significantly upregulated in the thalamus of ODS mice. ODS mice showed inabilities to perform motor tasks (Rotarod and Grip strength) and impairments in brainstem auditory evoked potentials. In conclusion, this murine model of ODS reproduces the demyelinating lesions observed in human pathology and raise new questions about the early role played by astrocytes or microglial cells in demyelination. Keywords: Osmotic Demyelination Syndrome, Astrocytopathy, oligodendrocytopathy, mouse model, microglial activation Conference: 12th National Congress of the Belgian Society for Neuroscience, Gent, Belgium, 22 May - 22 May, 2017. Presentation Type: Poster Presentation Topic: Disorders of the Nervous System Citation: Bouchat J, Couturier B, Gankam Kengne F, Poncelet L, Brion J, Gilloteaux J and Nicaise C (2019). Oligodendrocytopathy and astrocytopathy precede myelin loss and blood-brain barrier disruption in a mouse model of osmotic demyelination syndrome. Front. Neurosci. Conference Abstract: 12th National Congress of the Belgian Society for Neuroscience. doi: 10.3389/conf.fnins.2017.94.00115 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 16 Mar 2017; Published Online: 25 Jan 2019. * Correspondence: Mrs. Joanna Bouchat, UNamur, Laboratory of Neurodegenerescence and Regeneration, URPhyM - NARILIS, Namur, 5000, Belgium, joanna.bouchat@unamur.be Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Joanna Bouchat Bruno Couturier Fabrice Gankam Kengne Luc Poncelet Jean-Pierre Brion Jacques Gilloteaux Charles Nicaise Google Joanna Bouchat Bruno Couturier Fabrice Gankam Kengne Luc Poncelet Jean-Pierre Brion Jacques Gilloteaux Charles Nicaise Google Scholar Joanna Bouchat Bruno Couturier Fabrice Gankam Kengne Luc Poncelet Jean-Pierre Brion Jacques Gilloteaux Charles Nicaise PubMed Joanna Bouchat Bruno Couturier Fabrice Gankam Kengne Luc Poncelet Jean-Pierre Brion Jacques Gilloteaux Charles Nicaise Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.