title: Demyelination and axonal preservation in a transgenic mouse model of Pelizaeus-Merzbacher disease.
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.
authors.affiliation: Institute of Comparative Medicine, University of Glasgow, Scotland, UK. j.edgar@vet.gla.ac.uk
authors.forename: Julia M
authors.initials: JM
authors.lastname: Edgar
authors.forename: Mailis C
authors.initials: MC
authors.lastname: McCulloch
authors.forename: Paul
authors.initials: P
authors.lastname: Montague
authors.forename: Angus M
authors.initials: AM
authors.lastname: Brown
authors.forename: Sebastian
authors.initials: S
authors.lastname: Thilemann
authors.forename: Laura
authors.initials: L
authors.lastname: Pratola
authors.forename: Fredrik I
authors.initials: FI
authors.lastname: Gruenenfelder
authors.forename: Ian R
authors.initials: IR
authors.lastname: Griffiths
authors.forename: Klaus-Armin
authors.initials: KA
authors.lastname: Nave
mesh_terms: D000818:Animals; D001370:Axonal Transport / Q000502:physiology*; D001369:Axons / Q000502:physiology*; D003711:Demyelinating Diseases; D004195:Disease Models, Animal; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D018991:Myelin Proteolipid Protein / Q000235:genetics; D009900:Optic Nerve / Q000473:pathology / Q000503:physiopathology; D020371:Pelizaeus-Merzbacher Disease / Q000473:pathology*
chemical_list: D018991:Myelin Proteolipid Protein; C047516:Plp1 protein, mouse