Tauroursodeoxycholic Acid Improves Motor Symptoms in a Mouse Model of Parkinson’s Disease

Alexandra Isabel Rosa, Sara Duarte-Silva, Anabela Silva-Fernandes, Maria João Nunes, Andreia Neves Carvalho, Elsa Rodrigues, Maria João Gama, Cecília Maria Pereira Rodrigues, Patrícia Maciel, Margarida Castro-Caldas

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)9139-9155
Number of pages17
JournalMolecular Neurobiology
Volume55
Issue number12
DOIs
Publication statusPublished - 1 Dec 2018

Fingerprint

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
Parkinson Disease
Tremor
Gait
Foot
Aptitude
Parkinsonian Disorders
tauroursodeoxycholic acid
Bile Acids and Salts
Adhesives
Disease Progression
Adenosine Triphosphate
Clinical Trials
Phenotype

Keywords

  • Behavioral tests
  • MPTP
  • Neuroinflammation
  • Parkinson’s disease
  • TUDCA

Cite this

Rosa, 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, 55(12), 9139-9155. https://doi.org/10.1007/s12035-018-1062-4
Rosa, Alexandra Isabel ; Duarte-Silva, Sara ; Silva-Fernandes, Anabela ; Nunes, Maria João ; Carvalho, Andreia Neves ; Rodrigues, Elsa ; Gama, Maria João ; Rodrigues, Cecília Maria Pereira ; Maciel, Patrícia ; Castro-Caldas, Margarida. / Tauroursodeoxycholic Acid Improves Motor Symptoms in a Mouse Model of Parkinson’s Disease. In: Molecular Neurobiology. 2018 ; Vol. 55, No. 12. pp. 9139-9155.
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Rosa, AI, Duarte-Silva, S, Silva-Fernandes, A, Nunes, MJ, Carvalho, AN, Rodrigues, E, Gama, MJ, Rodrigues, CMP, Maciel, P & Castro-Caldas, M 2018, 'Tauroursodeoxycholic Acid Improves Motor Symptoms in a Mouse Model of Parkinson’s Disease', Molecular Neurobiology, vol. 55, no. 12, pp. 9139-9155. https://doi.org/10.1007/s12035-018-1062-4

Tauroursodeoxycholic Acid Improves Motor Symptoms in a Mouse Model of Parkinson’s Disease. / Rosa, Alexandra Isabel; Duarte-Silva, Sara; Silva-Fernandes, Anabela; Nunes, Maria João; Carvalho, Andreia Neves; Rodrigues, Elsa; Gama, Maria João; Rodrigues, Cecília Maria Pereira; Maciel, Patrícia; Castro-Caldas, Margarida.

In: Molecular Neurobiology, Vol. 55, No. 12, 01.12.2018, p. 9139-9155.

Research output: Contribution to journalArticle

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Rosa AI, Duarte-Silva S, Silva-Fernandes A, Nunes MJ, Carvalho AN, Rodrigues E et al. Tauroursodeoxycholic Acid Improves Motor Symptoms in a Mouse Model of Parkinson’s Disease. Molecular Neurobiology. 2018 Dec 1;55(12):9139-9155. https://doi.org/10.1007/s12035-018-1062-4