Please use this identifier to cite or link to this item:

Full metadata record
DC FieldValueLanguage
dc.contributor.authorSilva, Sara Carina Duartepor
dc.contributor.authorCarvalho, Andreia Alexandra Nevespor
dc.contributor.authorCunha, Carina Isabel Soarespor
dc.contributor.authorSilva, Joana M.por
dc.contributor.authorCastro, Andreia Cristiana Teixeirapor
dc.contributor.authorVieira, Ritapor
dc.contributor.authorFernandes, Anabela Silvapor
dc.contributor.authorMaciel, P.por
dc.identifier.citationDuarte‐Silva, S., Neves‐Carvalho, A., Soares‐Cunha, C., Silva, J. M., Teixeira‐Castro, A., Vieira, R., ... & Maciel, P. (2018). Neuroprotective effects of creatine in the CMVMJD135 mouse model of spinocerebellar ataxia type 3. Movement Disorders, 33(5), 815-826por
dc.description.abstractBackground and Objective: Mitochondrial dysfunction has been implicated in several neurodegenerative diseases. Creatine administration increases concentration of the energy buffer phosphocreatine, exerting protective effects in the brain. We evaluate whether a creatine‐enriched diet would be beneficial for a mouse model of spinocerebellar ataxia type 3, a genetically defined neurodegenerative disease for which no treatment is available. Methods: We performed 2 independent preclinical trials using the CMVMJD135 mouse model (treating 2 groups of animals with different disease severity) and wild‐type mice, to which 2% creatine was provided for 19 (preclinical trial 1) or 29 (preclinical trial 2) weeks, starting at a presymptomatic age. Motor behavior was evaluated at several time points from 5 to 34 weeks of age, and neuropathological studies were performed at the end of each trial. Results: Creatine supplementation led to an overall improvement in the motor phenotype of CMVMJD135 mice in both trials, rescuing motor balance and coordination and also restored brain weight, mitigated astrogliosis, and preserved Calbindin‐positive cells in the cerebellum. Moreover, a reduction of mutant ataxin‐3 aggregates occurred despite maintained steady‐state levels of the protein and the absence of autophagy activation. Creatine treatment also restored the expression of the mitochondrial mass marker Porin and reduced the expression of antioxidant enzymes Heme oxygenase 1 (HO1) and NAD(P)H Quinone Dehydrogenase 1 (NQO1), suggesting a beneficial effect at the level of mitochondria and oxidative stress. Conclusions: Creatine slows disease progression and improves motor dysfunction as well as ameliorates neuropathology of the CMVMJD135 animals, supporting this as a useful strategy to slow the progression of spinocerebellar ataxia type 3.por
dc.description.sponsorshipThis article has been developed under the scope of the project NORTE-01-0145-FEDER-000013, supported by the Northern Portugal Regional Operational Programme (NORTE 2020), under the Portugal 2020 Partnership Agreement, through the European Regional Development Fund (FEDER). This work has been funded by European Regional Development Fund funds, through the Competitiveness Factors Operational Programme, and by National funds, through the Foundation for Science and Technology, under the scope of the project POCI-01-0145-FEDER-007038 and through the project POCI-01-0145-FEDER016818 (PTDC/NEU-NMC/3648/2014) and fellowships (SFRH/BD/78388/2011 to S. D-S., SFRH/BD/51059/2010 to A.N.C., SFRH/BPD/91562/2012 to A.S-F., SFRH/BD/51992/2012 to C.S-C, SFRH/BD/88932/2012 to J.M.S.).por
dc.rightsembargoedAccess (1 Year)por
dc.subjectPreclinical trialpor
dc.subjectPolyglutamine diseasespor
dc.subjectMachado-Joseph diseasepor
dc.titleNeuroprotective Effects of Creatine in the CMVMJD135 Mouse Model of Spinocerebellar Ataxia Type 3por
dc.commentsauthor can archive post-print (ie final draft post-refereeing)por
dc.subject.fosCiências Médicas::Medicina Básicapor
dc.subject.wosScience & Technologypor
sdum.journalMovement Disorderspor
Appears in Collections:ICVS - Artigos em Revistas Internacionais com Referee

Files in This Item:
File Description SizeFormat 
Duarte-Silva2. Neuroprotective Effects of Creatine in the CMVMJD135 Mouse Model of Spinocerebellar Ataxia Type 3..pdf
  Restricted access
1,09 MBAdobe PDFView/Open

Partilhe no FacebookPartilhe no TwitterPartilhe no DeliciousPartilhe no LinkedInPartilhe no DiggAdicionar ao Google BookmarksPartilhe no MySpacePartilhe no Orkut
Exporte no formato BibTex mendeley Exporte no formato Endnote Adicione ao seu ORCID