Vesicular glutamate release from central axons contributes to myelin damage
dc.contributor.author | Doyle, S | |
dc.contributor.author | Hansen, Daniel Bloch | |
dc.contributor.author | Vella, J | |
dc.contributor.author | Bond, P | |
dc.contributor.author | Harper, Glenn | |
dc.contributor.author | Zammit, C | |
dc.contributor.author | Valentino, M | |
dc.contributor.author | fern, robert | |
dc.date.accessioned | 2018-10-16T15:00:22Z | |
dc.date.available | 2018-10-16T15:00:22Z | |
dc.date.issued | 2018-03-12 | |
dc.identifier.issn | 2041-1723 | |
dc.identifier.issn | 2041-1723 | |
dc.identifier.other | 1032 | |
dc.identifier.uri | http://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.extent | 0-0 | |
dc.format.medium | Electronic | |
dc.language | en | |
dc.language.iso | en | |
dc.publisher | Nature Publishing Group | |
dc.subject | Animals | |
dc.subject | Axons | |
dc.subject | Cytoplasmic Vesicles | |
dc.subject | Female | |
dc.subject | Glutamic Acid | |
dc.subject | Humans | |
dc.subject | Ischemia | |
dc.subject | Male | |
dc.subject | Mice | |
dc.subject | Mice, Inbred C57BL | |
dc.subject | Myelin Sheath | |
dc.subject | Rats | |
dc.subject | Rats, Wistar | |
dc.subject | Receptors, N-Methyl-D-Aspartate | |
dc.title | Vesicular glutamate release from central axons contributes to myelin damage | |
dc.type | journal-article | |
dc.type | Journal Article | |
dc.type | Research Support, Non-U.S. Gov't | |
plymouth.author-url | https://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000427121700007&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=11bb513d99f797142bcfeffcc58ea008 | |
plymouth.issue | 1 | |
plymouth.volume | 9 | |
plymouth.publication-status | Published online | |
plymouth.journal | Nature Communications | |
dc.identifier.doi | 10.1038/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.place | England | |
dcterms.dateAccepted | 2018-02-13 | |
dc.identifier.eissn | 2041-1723 | |
dc.rights.embargoperiod | Not known | |
rioxxterms.versionofrecord | 10.1038/s41467-018-03427-1 | |
rioxxterms.licenseref.uri | http://www.rioxx.net/licenses/all-rights-reserved | |
rioxxterms.licenseref.startdate | 2018-03-12 | |
rioxxterms.type | Journal Article/Review | |
plymouth.funder | Ion homeostasis in optic nerve astrocytes::BBSRC |