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dc.contributor.authorGiorgi-Coll, Susanen
dc.contributor.authorAmaral, AIen
dc.contributor.authorHutchinson, Peteren
dc.contributor.authorKotter, Marken
dc.contributor.authorCarpenter, Kerien
dc.date.accessioned2017-06-13T11:16:38Z
dc.date.available2017-06-13T11:16:38Z
dc.date.issued2017-04-21en
dc.identifier.issn2045-2322
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/264743
dc.description.abstractMitochondrial dysfunction, the inability to efficiently utilise metabolic fuels and oxygen, contributes to pathological changes following traumatic spinal cord or traumatic brain injury (TBI). In the present study, we tested the hypothesis that succinate supplementation can improve cellular energy state under metabolically stressed conditions in a robust, reductionist in vitro model of mitochondrial dysfunction in which primary mixed glial cultures (astrocytes, microglia and oligodendrocytes) were exposed to the mitochondrial complex I inhibitor rotenone. Cellular response was determined by measuring intracellular ATP, extracellular metabolites (glucose, lactate, pyruvate), and oxygen consumption rate (OCR). Rotenone produced no significant changes in glial ATP levels. However, it induced metabolic deficits as evidenced by lactate/pyruvate ratio (LPR) elevation (a clinically-established biomarker for poor outcome in TBI) and decrease in OCR. Succinate addition partially ameliorated these metabolic deficits. We conclude that succinate can improve glial oxidative metabolism, consistent our previous findings in TBI patients' brains. The mixed glial cellular model may be useful in developing therapeutic strategies for conditions involving mitochondrial dysfunction, such as TBI.
dc.languageengen
dc.language.isoenen
dc.publisherNature Publishing Group
dc.rightsAttribution 4.0 Internationalen
dc.rightsAttribution 4.0 Internationalen
dc.rightsAttribution 4.0 Internationalen
dc.rightsAttribution 4.0 Internationalen
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en
dc.titleSuccinate supplementation improves metabolic performance of mixed glial cell cultures with mitochondrial dysfunctionen
dc.typeArticle
prism.issueIdentifier1en
prism.number1003en
prism.publicationDate2017en
prism.publicationNameScientific Reportsen
prism.volume7en
dc.identifier.doi10.17863/CAM.10340
dcterms.dateAccepted2017-03-27en
rioxxterms.versionofrecord10.1038/s41598-017-01149-wen
rioxxterms.versionVoRen
rioxxterms.licenseref.urihttp://creativecommons.org/licenses/by/4.0/en
rioxxterms.licenseref.startdate2017-04-21en
dc.contributor.orcidGiorgi-Coll, Susan [0000-0002-9367-9408]
dc.contributor.orcidHutchinson, Peter [0000-0002-2796-1835]
dc.contributor.orcidKotter, Mark [0000-0001-5145-7199]
dc.contributor.orcidCarpenter, Keri [0000-0001-8236-7727]
dc.identifier.eissn2045-2322
rioxxterms.typeJournal Article/Reviewen
pubs.funder-project-idMRC (G1002277)
pubs.funder-project-idTCC (NIHR-RP-R3-12-013)


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Attribution 4.0 International
Except where otherwise noted, this item's licence is described as Attribution 4.0 International