Demyelination and axonal preservation in a transgenic mouse model of Pelizaeus-Merzbacher disease

Edgar, J.M. , McCulloch, M.C., Montague, P., Brown, A., Thilemann, S., Pratola, L., Gruenenfelder, F.I., Griffiths, I. and Nave, K.A. (2010) Demyelination and axonal preservation in a transgenic mouse model of Pelizaeus-Merzbacher disease. EMBO Molecular Medicine, 2(2), pp. 42-50. (doi: 10.1002/emmm.200900057)

Abstract

It is widely thought that demyelination contributes to the degeneration of axons and, in combination with acute inflammatory injury, is responsible for progressive axonal loss and persistent clinical disability in inflammatory demyelinating disease. In this study we sought to characterize the relationship between demyelination, inflammation and axonal transport changes using a Plp1-transgenic mouse model of Pelizaeus-Merzbacher disease. In the optic pathway of this non-immune mediated model of demyelination, myelin loss progresses from the optic nerve head towards the brain, over a period of months. Axonal transport is functionally perturbed at sites associated with local inflammation and 'damaged' myelin. Surprisingly, where demyelination is complete, naked axons appear well preserved despite a significant reduction of axonal transport. Our results suggest that neuroinflammation and/or oligodendrocyte dysfunction are more deleterious for axonal health than demyelination per se, at least in the short term

• Item Type: Articles
• Keywords: Animals Axonal Transport Axons Brain Demyelinating Diseases Disease Models,Animal genetics Humans Inflammation injuries Mice Mice,Transgenic Myelin Proteolipid Protein Optic Nerve pathology Pelizaeus-Merzbacher Disease physiology physiopathology Research Scotland
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Montague, Dr Paul and McCulloch, Mrs Maj-Lis and Edgar, Professor Julia and Griffiths, Prof Ian
• Authors: Edgar, J.M., McCulloch, M.C., Montague, P., Brown, A., Thilemann, S., Pratola, L., Gruenenfelder, F.I., Griffiths, I., and Nave, K.A.
• College/School: College of Medical Veterinary and Life Sciences > School of Infection & Immunity
• Journal Name: EMBO Molecular Medicine
• Publisher: Wiley
• ISSN: 1757-4676
• ISSN (Online): 1757-4684
• Published Online: 20 January 2010
• Copyright Holders: Copyright © 2010 EMBO Molecular Medicine
• First Published: First published in EMBO Molecular Medicine 2(2):42-50
• Publisher Policy: Reproduced in accordance with the copyright policy of the publisher