Please use this identifier to cite or link to this item: https://hdl.handle.net/10316/108048
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dc.contributor.authorDuarte, Ana I.-
dc.contributor.authorSjögren, Marie-
dc.contributor.authorSantos, Maria S.-
dc.contributor.authorOliveira, Catarina R.-
dc.contributor.authorMoreira, Paula I.-
dc.contributor.authorBjörkqvist, Maria-
dc.date.accessioned2023-08-07T14:43:44Z-
dc.date.available2023-08-07T14:43:44Z-
dc.date.issued2018-06-12-
dc.identifier.issn2045-2322pt
dc.identifier.urihttps://hdl.handle.net/10316/108048-
dc.description.abstractNeuronal loss alongside altered energy metabolism, are key features of Huntington's disease (HD) pathology. The orexigenic gut-peptide hormone ghrelin is known to stimulate appetite and affect whole body energy metabolism. Liraglutide is an efficient anti-type 2 diabetes incretin drug, with neuroprotective effects alongside anorectic properties. Combining liraglutide with the orexigenic peptide ghrelin may potentially promote brain/cognitive function in HD. The R6/2 mouse model of HD exhibits progressive central pathology, weight loss, deranged glucose metabolism, skeletal muscle atrophy and altered body composition. In this study, we targeted energy metabolism in R6/2 mice using a co-administration of liraglutide and ghrelin. We investigated their effect on brain cortical hormone-mediated intracellular signalling pathways, metabolic and apoptotic markers, and the impact on motor function in HD. We here demonstrate that liraglutide, alone or together with ghrelin (subcutaneous daily injections of 150 µg/kg (ghrelin) and 0.2 mg/kg (liraglutide), for 2 weeks), normalized glucose homeostatic features in the R6/2 mouse, without substantially affecting body weight or body composition. Liraglutide alone decreased brain cortical active GLP-1 and IGF-1 levels in R6/2 mice, alongside higher ADP levels. Liraglutide plus ghrelin decreased brain insulin, lactate, AMP and cholesterol levels in R6/2 mice. Taken together, our findings encourage further studies targeting energy metabolism in HD.pt
dc.language.isoengpt
dc.publisherSpringer Naturept
dc.relationSeed Fund from European Huntington’s Disease Network (EHDN)pt
dc.relationSwedish Research Councilpt
dc.relationNeuro Swedenpt
dc.relationKocks Foundationpt
dc.relationPTDC/SAU-TOX/117481/2010pt
dc.relationSFRH/BPD/84473/2012pt
dc.relationEuropean funds from FEDER, through the Programa Operacional Factores de Competitividade – COMPETE 2020pt
dc.rightsopenAccesspt
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/pt
dc.subject.meshAnimalspt
dc.subject.meshBrainpt
dc.subject.meshDisease Models, Animalpt
dc.subject.meshDrug Therapy, Combinationpt
dc.subject.meshEnergy Metabolismpt
dc.subject.meshGhrelinpt
dc.subject.meshHumanspt
dc.subject.meshHuntington Diseasept
dc.subject.meshLiraglutidept
dc.subject.meshMalept
dc.subject.meshMicept
dc.subject.meshMice, Transgenicpt
dc.titleDual Therapy with Liraglutide and Ghrelin Promotes Brain and Peripheral Energy Metabolism in the R6/2 Mouse Model of Huntington's Diseasept
dc.typearticle-
degois.publication.firstPage8961pt
degois.publication.issue1pt
degois.publication.titleScientific Reportspt
dc.peerreviewedyespt
dc.identifier.doi10.1038/s41598-018-27121-wpt
degois.publication.volume8pt
dc.date.embargo2018-06-12*
uc.date.periodoEmbargo0pt
item.languageiso639-1en-
item.fulltextCom Texto completo-
item.grantfulltextopen-
item.openairecristypehttp://purl.org/coar/resource_type/c_18cf-
item.openairetypearticle-
item.cerifentitytypePublications-
crisitem.author.researchunitCNC - Center for Neuroscience and Cell Biology-
crisitem.author.researchunitCNC - Center for Neuroscience and Cell Biology-
crisitem.author.researchunitCNC - Center for Neuroscience and Cell Biology-
crisitem.author.orcid0000-0002-6881-9392-
crisitem.author.orcid0000-0001-6942-4328-
crisitem.author.orcid0000-0001-5177-6747-
Appears in Collections:FCTUC Ciências da Vida - Artigos em Revistas Internacionais
IIIUC - Artigos em Revistas Internacionais
FMUC Medicina - Artigos em Revistas Internacionais
I&D CNC - Artigos em Revistas Internacionais
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This item is licensed under a Creative Commons License Creative Commons