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dc.contributor.authorLeikas J V
dc.contributor.authorKohtala S
dc.contributor.authorTheilmann W
dc.contributor.authorJalkanen A J
dc.contributor.authorForsberg M M
dc.contributor.authorRantamäki T
dc.date.accessioned2017-12-01T11:11:02Z
dc.date.available2017-12-01T11:11:02Z
dc.date.issued2017
dc.identifier.urihttps://erepo.uef.fi/handle/123456789/5046
dc.description.abstractParkinson's disease (PD) is a progressive neurodegenerative movement disorder primarily affecting the nigrostriatal dopaminergic system. The link between heightened activity of glycogen synthase kinase 3β (GSK3β) and neurodegene-rative processes has encouraged investigation into the potential disease-modifying effects of novel GSK3β inhibitors in experimental models of PD. Therefore, the intriguing ability of several anesthetics to readily inhibit GSK3β within the cortex and hippocampus led us to investigate the effects of brief isoflurane anesthesia on striatal GSK3β signaling in naïve rats and in a rat model of early-stage PD. Deep but brief (20-min) isoflurane anesthesia exposure increased the phosphorylation of GSK3β at the inhibitory Ser9 residue, and induced phosphorylation of AKTThr308 (protein kinase B; negative regulator of GSK3β) in the striatum of naïve rats and rats with unilateral striatal 6-hydroxydopamine (6-OHDA) lesion. The 6-OHDA protocol produced gradual functional deficiency within the nigrostriatal pathway, reflected as a preference for using the limb ipsilateral to the lesioned striatum at 2 weeks post 6-OHDA. Interestingly, such motor impairment was not observed in animals exposed to four consecutive isoflurane treatments (20-min anesthesia every 48 h; treatments started 7 days after 6-OHDA delivery). However, isoflurane had no effect on striatal or nigral tyrosine hydroxylase (a marker of dopaminergic neurons) protein levels. This brief report provides promising results regarding the therapeutic potential and neurobiological mechanisms of anesthetics in experimental models of PD and guides development of novel disease-modifying therapies.en
dc.language.isoENen
dc.publisherWiley-Blackwellen
dc.relation.ispartofseriesJOURNAL OF NEUROCHEMISTRYen
dc.relation.urihttp://dx.doi.org/10.1111/jnc.14066en
dc.rightsCC BY-NC-ND https://creativecommons.org/licenses/by-nc-nd/4.0/en
dc.subjectanesthesiaen
dc.subjectdopamineen
dc.subjectneurodegenerationen
dc.subjectphosphorylationen
dc.subjectsensorimotor testen
dc.titleBrief isoflurane anesthesia regulates striatal AKT-GSK3ß signaling and ameliorates motor deficits in a rat model of early-stage Parkinson's diseaseen
dc.description.versionpublished versionen
dc.contributor.departmentSchool of Pharmacy, Activitiesen
uef.solecris.id48860870en
dc.type.publicationinfo:eu-repo/semantics/articleen
dc.rights.accessrights© Authorsen
dc.relation.doi10.1111/jnc.14066en
dc.description.reviewstatuspeerRevieweden
dc.format.pagerange456-463en
dc.publisher.countryBritanniaen
dc.relation.issn0022-3042en
dc.relation.issue3en
dc.relation.volume142en
dc.rights.accesslevelopenAccessen
dc.type.okmA1en
dc.type.versioninfo:eu-repo/semantics/publishedVersionen
uef.solecris.openaccessHybridijulkaisukanavassa ilmestynyt avoin julkaisu


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