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dc.contributor.authorKostovski, Emil
dc.contributor.authorFrigato, E
dc.contributor.authorSavikj, Mladen
dc.contributor.authorDahm, Anders Erik A
dc.contributor.authorSandset, Per Morten
dc.contributor.authorMowinckel, Marie-Christine
dc.contributor.authorSkretting, Grethe
dc.contributor.authorØsterud, Bjarne
dc.contributor.authorBertolucci, C
dc.contributor.authorIversen, Per Ole
dc.date.accessioned2019-04-09T11:07:04Z
dc.date.available2019-04-09T11:07:04Z
dc.date.issued2018-07-09
dc.description.abstract<i>Study design</i>: Crossover double blind, randomized placebo-controlled trial.<p> <p><i>Objectives</i>: Circadian oscillators are located both in the brain and in peripheral organs. Melatonin, the main brain-derived hormone governing circadian variations, is highly associated with daylight patterns. However, in subjects with tetraplegia the melatonin levels are blunted. Here we studied peripheral oscillators in peripheral blood mononuclear cells (PBMCs) in males with tetraplegia by examining how exogenous melatonin may influence the expression of clock gene mRNAs.<p> <p><i>Setting</i>: Sunnaas Rehabilitation Hospital, Nesoddtangen, Norway.<p> <p><i>Methods</i>: Six males with tetraplegia received 2 mg of melatonin or placebo 4 days before the study period. We also included six able-bodied men sleeping or kept awake during the night. Plasma samples were collected four times during a 24-h period. The mRNA expression levels of the clock genes <i>PER1</i>, <i>PER2</i>, <i>BMAL1</i>, and <i>REV-ERBα </i>were quantified in PBMCs using quantitative RT-PCR.<p> <p><i>Results</i>: The mRNA expression levels of <i>PER-1 and –2</i> and <i>REV-ERBα</i> were increased at 04:00 h compared with the ablebodied controls (<i>p</i> < 0.05). Melatonin supplementation changed mRNA peak-time toward the time of supplementation.<p> <p><i>Conclusions</i>: Several peripheral clock genes displayed distorted expression levels in tetraplegia. Supplementation with melatonin changed the mRNA expression levels of these genes toward those observed among able-bodied.en_US
dc.description.sponsorshipThrone Holst Foundation Sunnaas Rehabilitation hospital University of Ferraraen_US
dc.descriptionAccepted manuscript version. Published version available at <a href=https://doi.org/10.1038/s41393-018-0176-x>https://doi.org/10.1038/s41393-018-0176-x. </a>en_US
dc.identifier.citationKostovski, E., Frigato, E., Savikj, M., Dahm, A.E.A., Sandset, P.M., Mowinckel, M.C. ... Iversen, P.O. (2018). Normalization of disrupted clock gene expression in males with tetraplegia: a crossover randomized placebo-controlled trial of melatonin supplementation. <i>Spinal Cord</i>, 56, 1076-1083. https://doi.org/10.1038/s41393-018-0176-xen_US
dc.identifier.cristinIDFRIDAID 1599743
dc.identifier.doi10.1038/s41393-018-0176-x
dc.identifier.issn1362-4393
dc.identifier.issn1476-5624
dc.identifier.urihttps://hdl.handle.net/10037/15181
dc.language.isoengen_US
dc.publisherSpringer Natureen_US
dc.relation.journalSpinal Cord
dc.rights.accessRightsopenAccessen_US
dc.subjectVDP::Medical disciplines: 700::Basic medical, dental and veterinary science disciplines: 710en_US
dc.subjectVDP::Medisinske Fag: 700::Basale medisinske, odontologiske og veterinærmedisinske fag: 710en_US
dc.titleNormalization of disrupted clock gene expression in males with tetraplegia: a crossover randomized placebo-controlled trial of melatonin supplementationen_US
dc.typeJournal articleen_US
dc.typeTidsskriftartikkelen_US
dc.typePeer revieweden_US


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