Utilize este identificador para referenciar este registo: https://hdl.handle.net/1822/57822

TítuloNeuroprotective effects of creatine in the CMVMJD135 mouse model of Spinocerebellar Ataxia type 3
Autor(es)Silva, Sara Carina Duarte
Carvalho, Andreia Alexandra Neves
Cunha, Carina Isabel Soares
Silva, Joana M.
Castro, Andreia Cristiana Teixeira
Vieira, Rita
Fernandes, Anabela Silva
Maciel, P.
Palavras-chaveCreatine
Preclinical trial
Polyglutamine diseases
Machado-Joseph disease
Therapy
DataMai-2018
EditoraWiley
RevistaMovement Disorders
CitaçãoDuarte‐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), 815-826
Resumo(s)Background 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.
TipoArtigo
URIhttps://hdl.handle.net/1822/57822
DOI10.1002/mds.27292
ISSN0885-3185
e-ISSN1531-8257
Versão da editorahttps://onlinelibrary.wiley.com/doi/full/10.1002/mds.27292
Arbitragem científicayes
AcessoAcesso aberto
Aparece nas coleções:ICVS - Artigos em revistas internacionais / Papers in international journals

Ficheiros deste registo:
Ficheiro Descrição TamanhoFormato 
Duarte-Silva2. Neuroprotective Effects of Creatine in the CMVMJD135 Mouse Model of Spinocerebellar Ataxia Type 3..pdf
Acesso restrito!
1,09 MBAdobe PDFVer/Abrir

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