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dc.contributor.authorPocivavsek, A.
dc.contributor.authorBaratta, A.M.
dc.contributor.authorMong, J.A.
dc.date.accessioned2019-10-08T19:43:54Z
dc.date.available2019-10-08T19:43:54Z
dc.date.issued2017
dc.identifier.urihttps://www.scopus.com/inward/record.uri?eid=2-s2.0-85040841372&doi=10.1093%2fsleep%2fzsx141&partnerID=40&md5=74308e8d84391e7ebff9bc677a75e358
dc.identifier.urihttp://hdl.handle.net/10713/11146
dc.description.abstractStudy Objectives: Tryptophan metabolism via the kynurenine pathway may represent a key molecular link between sleep loss and cognitive dysfunction. Modest increases in the kynurenine pathway metabolite kynurenic acid (KYNA), which acts as an antagonist at N-methyl-d-aspartate and α7 nicotinic acetylcholine receptors in the brain, result in cognitive impairments. As glutamatergic and cholinergic neurotransmissions are critically involved in modulation of sleep, our current experiments tested the hypothesis that elevated KYNA adversely impacts sleep quality. Methods: Adult male Wistar rats were treated with vehicle (saline) and kynurenine (25, 50, 100, and 250 mg/kg), the direct bioprecursor of KYNA, intraperitoneally at zeitgeber time (ZT) 0 to rapidly increase brain KYNA. Levels of KYNA in the brainstem, cortex, and hippocampus were determined at ZT 0, ZT 2, and ZT 4, respectively. Analyses of vigilance state-related parameters categorized as wake, rapid eye movement (REM), and non-REM (NREM) as well as spectra power analysis during NREM and REM were assessed during the light phase. Separate animals were tested in the passive avoidance paradigm, testing contextual memory. Results: When KYNA levels were elevated in the brain, total REM duration was reduced and total wake duration was increased. REM and wake architecture, assessed as number of vigilance state bouts and average duration of each bout, and theta power during REM were significantly impacted. Kynurenine challenge impaired performance in the hippocampal-dependent contextual memory task. Conclusions: Our results introduce kynurenine pathway metabolism and formation of KYNA as a novel molecular target contributing to sleep disruptions and cognitive impairments.en_US
dc.description.urihttps://doi.org/10.1093/sleep/zsx141en_US
dc.language.isoen_USen_US
dc.publisherOxford Academic
dc.relation.ispartofSleep
dc.subjectbasic scienceen_US
dc.subjectcognitive functionen_US
dc.subjecthippocampusen_US
dc.subjectkynurenic aciden_US
dc.subjectneuropharmacologyen_US
dc.subjectREM sleepen_US
dc.subjecttryptophanen_US
dc.subjectα7 nicotinic acetylcholine receptoren_US
dc.titleAcute Kynurenine Challenge Disrupts Sleep-Wake Architecture and Impairs Contextual Memory in Adult Ratsen_US
dc.typeArticleen_US
dc.identifier.doi10.1093/sleep/zsx141
dc.identifier.pmid29029302


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