Utilize este identificador para referenciar este registo: http://hdl.handle.net/1822/57940

TítuloTauroursodeoxycholic Acid Improves Motor Symptoms in a Mouse Model of Parkinson's Disease
Autor(es)Rosa, Alexandra Isabel
Silva, Sara Carina Duarte
Silva-Fernandes, Anabela
Nunes, Maria João
Carvalho, Andreia Neves
Rodrigues, Elsa
Gama, Maria João
Rodrigues, Cecília Maria Pereira
Maciel, P.
Castro-Caldas, Margarida
Palavras-chaveParkinson’s disease
MPTP
TUDCA
Behavioral tests
Neuroinflammation
DataDez-2018
EditoraSpringer
RevistaMolecular Neurobiology
CitaçãoRosa, A. I., Duarte-Silva, S., Silva-Fernandes, A., Nunes, M. J., Carvalho, A. N., Rodrigues, E., ... & Castro-Caldas, M. (2018). Tauroursodeoxycholic Acid Improves Motor Symptoms in a Mouse Model of Parkinson’s Disease. Molecular neurobiology, 1-17
Resumo(s)Parkinson's disease (PD) is characterized by severe motor symptoms, and currently there is no treatment that retards disease progression or reverses damage prior to the time of clinical diagnosis. Tauroursodeoxycholic acid (TUDCA) is neuroprotective in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of PD; however, its effect in PD motor symptoms has never been addressed. In the present work, an extensive behavior analysis was performed to better characterize the MPTP model of PD and to evaluate the effects of TUDCA in the prevention/improvement of mice phenotype. MPTP induced significant alterations in general motor performance paradigms, including increased latency in the motor swimming, adhesive removal and pole tests, as well as altered gait, foot dragging, and tremors. TUDCA administration, either before or after MPTP, significantly reduced the swimming latency, improved gait quality, and decreased foot dragging. Importantly, TUDCA was also effective in the prevention of typical parkinsonian symptoms such as spontaneous activity, ability to initiate movement and tremors. Accordingly, TUDCA prevented MPTP-induced decrease of dopaminergic fibers and ATP levels, mitochondrial dysfunction and neuroinflammation. Overall, MPTP-injected mice presented motor symptoms that are aggravated throughout time, resembling human parkinsonism, whereas PD motor symptoms were absent or mild in TUDCA-treated animals, and no aggravation was observed in any parameter. The thorough demonstration of improvement of PD symptoms together with the demonstration of the pathways triggered by TUDCA supports a subsequent clinical trial in humans and future validation of the application of this bile acid in PD.
Tipoarticle
URIhttp://hdl.handle.net/1822/57940
DOI10.1007/s12035-018-1062-4
ISSN0893-7648
e-ISSN1559-1182
Versão da editorahttps://link.springer.com/article/10.1007/s12035-018-1062-4
Arbitragem científicayes
AcessoembargoedAccess (1 Year)
Aparece nas coleções:ICVS - Artigos em Revistas Internacionais com Referee


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