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dc.contributor.authorDoyle, S
dc.contributor.authorHansen, DB
dc.contributor.authorVella, J
dc.contributor.authorBond, P
dc.contributor.authorHarper, G
dc.contributor.authorZammit, C
dc.contributor.authorValentino, M
dc.contributor.authorFern, R
dc.date.accessioned2018-10-16T15:00:22Z
dc.date.available2018-10-16T15:00:22Z
dc.date.issued2018-03-12
dc.identifier.issn2041-1723
dc.identifier.issn2041-1723
dc.identifier.other1032
dc.identifier.urihttp://hdl.handle.net/10026.1/12557
dc.description.abstract

<jats:title>Abstract</jats:title><jats:p>The axon myelin sheath is prone to injury associated with <jats:italic>N</jats:italic>-methyl-<jats:sc>d</jats:sc>-aspartate (NMDA)-type glutamate receptor activation but the source of glutamate in this context is unknown. Myelin damage results in permanent action potential loss and severe functional deficit in the white matter of the CNS, for example in ischemic stroke. Here, we show that in rats and mice, ischemic conditions trigger activation of myelinic NMDA receptors incorporating GluN2C/D subunits following release of axonal vesicular glutamate into the peri-axonal space under the myelin sheath. Glial sources of glutamate such as reverse transport did not contribute significantly to this phenomenon. We demonstrate selective myelin uptake and retention of a GluN2C/D NMDA receptor negative allosteric modulator that shields myelin from ischemic injury. The findings potentially support a rational approach toward a low-impact prophylactic therapy to protect patients at risk of stroke and other forms of excitotoxic injury.</jats:p>

dc.format.extent0-0
dc.format.mediumElectronic
dc.languageen
dc.language.isoen
dc.publisherNature Publishing Group
dc.subjectAnimals
dc.subjectAxons
dc.subjectCytoplasmic Vesicles
dc.subjectFemale
dc.subjectGlutamic Acid
dc.subjectHumans
dc.subjectIschemia
dc.subjectMale
dc.subjectMice
dc.subjectMice, Inbred C57BL
dc.subjectMyelin Sheath
dc.subjectRats
dc.subjectRats, Wistar
dc.subjectReceptors, N-Methyl-D-Aspartate
dc.titleVesicular glutamate release from central axons contributes to myelin damage
dc.typejournal-article
dc.typeArticle
plymouth.author-urlhttps://www.ncbi.nlm.nih.gov/pubmed/29531223
plymouth.issue1
plymouth.volume9
plymouth.publication-statusPublished online
plymouth.journalNature Communications
dc.identifier.doi10.1038/s41467-018-03427-1
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/Faculty of Science and Engineering
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/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
dc.publisher.placeEngland
dcterms.dateAccepted2018-02-13
dc.identifier.eissn2041-1723
dc.rights.embargoperiodNot known
rioxxterms.versionofrecord10.1038/s41467-018-03427-1
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserved
rioxxterms.licenseref.startdate2018-03-12
rioxxterms.typeJournal Article/Review
plymouth.funderIon homeostasis in optic nerve astrocytes::BBSRC


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