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Dose-dependent effect of cannabinoid WIN-55,212-2 on myelin repair following a demyelinating insult

dc.contributor.authorTomas-Roig, J.
dc.contributor.authorAgbemenyah, H. Y.
dc.contributor.authorCelarain, N.
dc.contributor.authorQuintana, E.
dc.contributor.authorRamió-Torrentà, Ll.
dc.contributor.authorHavemann-Reinecke, U.
dc.date.accessioned2020-01-20T09:00:04Z
dc.date.available2020-01-20T09:00:04Z
dc.date.issued2020de
dc.relation.ISSN2045-2322de
dc.identifier.urihttp://resolver.sub.uni-goettingen.de/purl?gs-1/17128
dc.description.abstractDysfunctions in the endocannabinoid system have been associated with experimental animal models and multiple sclerosis patients. Interestingly, the endocannabinoid system has been reported to confer neuroprotection against demyelination. The present study aims to assess the effects of the cannabinoid agonist WIN-55,212-2 in cuprizone fed animals on myelin repair capacity. Animals exposed to cuprizone were simultaneously treated withWIN-55,212-2, behaviorally tested and finally the corpus callosum was exhaustively studied by Western blotting, qRT-PCR and a myelin staining procedure. We report that the long-term administration of WIN-55,212-2 reduced the global amount of CB1 protein. Histological analysis revealed clear demyelination after being fed cuprizone for three weeks. However, cuprizone-fed mice subjected to 0.5 mg/Kg of WIN-55,212-2 displayed no differences when compared to controls during demyelination, although there was a robust increase in the myelinated axons during the remyelination phase. These animals displayed better performance on contextual fear conditioning which was in turn non-attributable to an antinociceptive effect. In contrast, a 1 mg/Kg dosage caused a remarkable demyelination accompanied by limited potential for myelin repair. Upon drug administration while mice ongoing demyeliniation, the expression of Aif1 (microglia) and Gfap (astrocytes) followed a dose-dependent manner whereas the expression of both markers was apparently attenuated during remyelination. Treatment with vehicle or 0.5 mg/Kg of the drug during demyelination increased the expression of Pdgfra (oligodendrocyte precursor cells) but this did not occur when 1 mg/Kg was administered. In conclusion, the drug at 0.5 mg/Kg did not alter myelin architecture while 1 mg/Kg had a deleterious effect in this model.de
dc.description.sponsorshipOpen-Access-Publikationsfonds 2020
dc.language.isoengde
dc.rightsopenAccess
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.subjectcannabinoid; WIN-55;de
dc.subject.ddc573
dc.subject.ddc612
dc.titleDose-dependent effect of cannabinoid WIN-55,212-2 on myelin repair following a demyelinating insultde
dc.typejournalArticlede
dc.identifier.doi10.1038/s41598-019-57290-1
dc.type.versionpublishedVersionde
dc.relation.eISSN2045-2322
dc.bibliographicCitation.volume10de
dc.bibliographicCitation.issue1de
dc.type.subtypejournalArticle
dc.bibliographicCitation.articlenumber590de
dc.description.statuspeerReviewedde
dc.bibliographicCitation.journalScientific Reportsde


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