Brief isoflurane anesthesia regulates striatal AKT-GSK3 beta signaling and ameliorates motor deficits in a rat model of early-stage Parkinson's disease

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dc.contributor.author Leikas, Juuso V.
dc.contributor.author Kohtala, Samuel
dc.contributor.author Theilmann, Wiebke
dc.contributor.author Jalkanen, Aaro J.
dc.contributor.author Forsberg, Markus M.
dc.contributor.author Rantamaki, Tomi
dc.date.accessioned 2018-10-10T13:03:01Z
dc.date.available 2018-10-10T13:03:01Z
dc.date.issued 2017-08
dc.identifier.citation Leikas , J V , Kohtala , S , Theilmann , W , Jalkanen , A J , Forsberg , M M & Rantamaki , T 2017 , ' Brief isoflurane anesthesia regulates striatal AKT-GSK3 beta signaling and ameliorates motor deficits in a rat model of early-stage Parkinson's disease ' , Journal of Neurochemistry , vol. 142 , no. 3 , pp. 456-463 . https://doi.org/10.1111/jnc.14066
dc.identifier.other PURE: 87804354
dc.identifier.other PURE UUID: cfc2f9f1-1657-4a35-b3f4-083d7db05295
dc.identifier.other WOS: 000405768400010
dc.identifier.other Scopus: 85020713384
dc.identifier.other ORCID: /0000-0002-0052-1434/work/39203845
dc.identifier.other ORCID: /0000-0001-9249-085X/work/39206248
dc.identifier.uri http://hdl.handle.net/10138/248407
dc.description.abstract Parkinson's disease (PD) is a progressive neurodegenerative movement disorder primarily affecting the nigrostriatal dopaminergic system. The link between heightened activity of glycogen synthase kinase 3 beta (GSK313) and neurodegenerative processes has encouraged investigation into the potential disease-modifying effects of novel GSK3 beta inhibitors in experimental models of PD. Therefore, the intriguing ability of several anesthetics to readily inhibit GSK3 beta within the cortex and hippocampus led us to investigate the effects of brief isoflurane anesthesia on striatal GSK3 beta signaling in nave rats and in a rat model of early-stage PD. Deep but brief (20-min) isoflurane anesthesia exposure increased the phosphorylation of GSK3 beta at the inhibitory Ser9 residue, and induced phosphorylation of AKT(Thr308) (protein kinase B; negative regulator of GSK3 beta) in the striatum of naive 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.format.extent 8
dc.language.iso eng
dc.relation.ispartof Journal of Neurochemistry
dc.rights cc_by_nc_nd
dc.rights.uri info:eu-repo/semantics/openAccess
dc.subject anesthesia
dc.subject dopamine
dc.subject neurodegeneration
dc.subject phosphorylation
dc.subject sensorimotor test
dc.subject GLYCOGEN-SYNTHASE KINASE-3
dc.subject ELECTROCONVULSIVE SHOCK
dc.subject ALPHA-SYNUCLEIN
dc.subject DOPAMINE
dc.subject PHOSPHORYLATION
dc.subject PATHWAY
dc.subject BRAIN
dc.subject NEUROPROTECTION
dc.subject HIPPOCAMPUS
dc.subject INHIBITION
dc.subject 1182 Biochemistry, cell and molecular biology
dc.subject 3112 Neurosciences
dc.title Brief isoflurane anesthesia regulates striatal AKT-GSK3 beta signaling and ameliorates motor deficits in a rat model of early-stage Parkinson's disease en
dc.type Article
dc.contributor.organization Biosciences
dc.contributor.organization Laboratory of Neurotherapeutics
dc.description.reviewstatus Peer reviewed
dc.relation.doi https://doi.org/10.1111/jnc.14066
dc.relation.issn 0022-3042
dc.rights.accesslevel openAccess
dc.type.version publishedVersion

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