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dc.contributor.authorJackson, Jen
dc.contributor.authorBianco, Gen
dc.contributor.authorRosa, AOen
dc.contributor.authorCowan, Ken
dc.contributor.authorBond, Pen
dc.contributor.authorAnichtchik, Oen
dc.contributor.authorFern, Ren
dc.date.accessioned2018-01-30T11:26:45Z
dc.date.available2018-01-30T11:26:45Z
dc.date.issued2018-01-08en
dc.identifier.issn0894-1491en
dc.identifier.urihttp://hdl.handle.net/10026.1/10688
dc.description.abstract

Early white matter (WM) changes are common in dementia and may contribute to functional decline. We here examine this phenomenon in an induced dementia model for the first time. We report a novel and selective form of myelin injury as the first manifestation of tauopathy in the adult central nervous system. Myelin pathology rapidly followed the induction of a P301 tau mutation associated with fronto-temporal dementia in humans (rTG4510 line). Damage involved focal disruption of the ad-axonal myelin lamella and internal oligodendrocyte tongue process, followed by myelin remodeling with features of re-myelination that included myelin thinning and internodal shortening. The evolution of the re-myelinated phenotype was complete in the molecular layer of the dentate gyrus after 1 month and in the optic nerve (ON) after 9 months of transgene induction and proceeded in the absence of actual demyelination, reactive glial changes or inflammatory response. The initial rapid myelin pathology was associated with loss of WM function and performance decline in a novel recognition test and both these effects largely reversed during the myelin re-modeling phase. The initial phase of myelin injury was accompanied by disruption of the vesicle population present in the axoplasm of hippocampal and ON axons. Axoplasmic vesicle release is significant for the regulation of myelin plasticity and disruption of this pathway may underlie the myelin damage and remodeling evoked by tauopathy. WM dysfunction early in tauopathy will disorder neural circuits, the current findings suggest this event may make a significant contribution to early clinical deficit in dementia.

en
dc.language.isoenen
dc.publisherWileyen
dc.subjectaxonen
dc.subjectdementiaen
dc.subjectmyelinen
dc.subjectoligodendrocyteen
dc.subjectwhite matteren
dc.titleWhite matter tauopathy: Transient functional loss and novel myelin remodeling.en
dc.typeJournal Article
plymouth.author-urlhttps://www.ncbi.nlm.nih.gov/pubmed/29315804en
plymouth.publication-statusPublished onlineen
plymouth.journalGliaen
dc.identifier.doi10.1002/glia.23286en
plymouth.organisational-group/Plymouth
plymouth.organisational-group/Plymouth/Admin Group - REF
plymouth.organisational-group/Plymouth/Admin Group - REF/REF Admin Group - FoH
plymouth.organisational-group/Plymouth/Faculty of Health
plymouth.organisational-group/Plymouth/Faculty of Health/Peninsula Medical School
plymouth.organisational-group/Plymouth/REF 2021 Researchers by UoA
plymouth.organisational-group/Plymouth/REF 2021 Researchers by UoA/UoA01 Clinical Medicine
plymouth.organisational-group/Plymouth/REF 2021 Researchers by UoA/UoA01 Clinical Medicine/UoA01 Clinical Medicine
plymouth.organisational-group/Plymouth/Research Groups
plymouth.organisational-group/Plymouth/Research Groups/Institute of Translational and Stratified Medicine (ITSMED)
plymouth.organisational-group/Plymouth/Research Groups/Institute of Translational and Stratified Medicine (ITSMED)/CBR
plymouth.organisational-group/Plymouth/Users by role
plymouth.organisational-group/Plymouth/Users by role/Academics
dcterms.dateAccepted2017-12-11en
dc.rights.embargodate2019-01-08en
dc.identifier.eissn1098-1136en
dc.rights.embargoperiodNot knownen
rioxxterms.versionofrecord10.1002/glia.23286en
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserveden
rioxxterms.licenseref.startdate2018-01-08en
rioxxterms.typeJournal Article/Reviewen
plymouth.funderIon homeostasis in optic nerve astrocytes::BBSRCen


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