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

Autor: Alexandra Isabel Rosa, Andreia Neves Carvalho, Anabela Silva-Fernandes, Maria João Nunes, Patrícia Maciel, Margarida Castro-Caldas, Elsa Rodrigues, Maria João Gama, Cecília M. P. Rodrigues, Sara Duarte-Silva
Přispěvatelé: DCV - Departamento de Ciências da Vida, UCIBIO - Applied Molecular Biosciences Unit, Universidade do Minho
Jazyk: angličtina
Rok vydání: 2018
Předmět:
Male
0301 basic medicine
Parkinson's disease
Neurology
Behavioral tests
Medicina Básica [Ciências Médicas]
Pharmacology
Mice
chemistry.chemical_compound
0302 clinical medicine
Neuroinflammation
Tremor
Homeostasis
Gait
Parkinsonism
MPTP
Dopaminergic
Parkinson Disease
TUDCA
Hindlimb
Mitochondria
3. Good health
Neuroprotective Agents
1-Methyl-4-phenyl-1
2
3
6-tetrahydropyridine
Ciências Médicas::Medicina Básica
Neuroglia
medicine.medical_specialty
Movement
Neuroscience (miscellaneous)
Motor Activity
Neuroprotection
Taurochenodeoxycholic Acid
03 medical and health sciences
Cellular and Molecular Neuroscience
SDG 3 - Good Health and Well-being
medicine
Animals
Inflammation
Science & Technology
business.industry
Tauroursodeoxycholic acid
medicine.disease
nervous system diseases
Mice
Inbred C57BL
Neostriatum
Disease Models
Animal
030104 developmental biology
chemistry
Nerve Degeneration
Parkinson’s disease
business
030217 neurology & neurosurgery
Zdroj: Repositório Científico de Acesso Aberto de Portugal
Repositório Científico de Acesso Aberto de Portugal (RCAAP)
instacron:RCAAP
Popis: 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.
National funds, through the Foundation for Science and Technology (Portugal) (FCT), under the scope of the projects PTDC/NEU-NMC/0248/2012, UID/DTP/04138/2013 and POCI-01-0145-FEDER-007038, and post-doctoral grants SFRH/BPD72891/2010 (to A.I.R.), SFRH/BPD/95855/2013 (to M.J.N.), SFRH/BPD/98023/2013 (to A.N.C.), SFRH/BPD/91562/2012 (to A.S.F.) and UMINHO/BI/248/2016 (to S.D.S.). This work has also been developed under the scope of the project NORTE-01-0145-FEDER-000013, supported by the Northern Portugal Regional Operational Program (NORTE 2020), under the Portugal 2020 Partnership Agreement, through the European Regional Development Fund (FEDER), and by FEDER funds, through the Competitiveness Factors Operational Program (COMPETE)
info:eu-repo/semantics/publishedVersion
Databáze: OpenAIRE
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