Tauroursodeoxycholic Acid Improves Motor Symptoms in a Mouse Model of Parkinson's Disease
Autor(a) principal: | |
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Data de Publicação: | 2018 |
Outros Autores: | , , , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
Texto Completo: | http://hdl.handle.net/1822/57940 |
Resumo: | 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. |
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Tauroursodeoxycholic Acid Improves Motor Symptoms in a Mouse Model of Parkinson's DiseaseParkinson’s diseaseMPTPTUDCABehavioral testsNeuroinflammationCiências Médicas::Medicina BásicaScience & TechnologyParkinson'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/publishedVersionSpringerUniversidade do MinhoRosa, Alexandra IsabelSilva, Sara Carina DuarteSilva-Fernandes, AnabelaNunes, Maria JoãoCarvalho, Andreia NevesRodrigues, ElsaGama, Maria JoãoRodrigues, Cecília Maria PereiraMaciel, P.Castro-Caldas, Margarida2018-122018-12-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/1822/57940engRosa, 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, 1-170893-76481559-118210.1007/s12035-018-1062-429651747https://link.springer.com/article/10.1007/s12035-018-1062-4info:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2023-07-21T12:07:37Zoai:repositorium.sdum.uminho.pt:1822/57940Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T18:58:38.646185Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse |
dc.title.none.fl_str_mv |
Tauroursodeoxycholic Acid Improves Motor Symptoms in a Mouse Model of Parkinson's Disease |
title |
Tauroursodeoxycholic Acid Improves Motor Symptoms in a Mouse Model of Parkinson's Disease |
spellingShingle |
Tauroursodeoxycholic Acid Improves Motor Symptoms in a Mouse Model of Parkinson's Disease Rosa, Alexandra Isabel Parkinson’s disease MPTP TUDCA Behavioral tests Neuroinflammation Ciências Médicas::Medicina Básica Science & Technology |
title_short |
Tauroursodeoxycholic Acid Improves Motor Symptoms in a Mouse Model of Parkinson's Disease |
title_full |
Tauroursodeoxycholic Acid Improves Motor Symptoms in a Mouse Model of Parkinson's Disease |
title_fullStr |
Tauroursodeoxycholic Acid Improves Motor Symptoms in a Mouse Model of Parkinson's Disease |
title_full_unstemmed |
Tauroursodeoxycholic Acid Improves Motor Symptoms in a Mouse Model of Parkinson's Disease |
title_sort |
Tauroursodeoxycholic Acid Improves Motor Symptoms in a Mouse Model of Parkinson's Disease |
author |
Rosa, Alexandra Isabel |
author_facet |
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 |
author_role |
author |
author2 |
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 |
author2_role |
author author author author author author author author author |
dc.contributor.none.fl_str_mv |
Universidade do Minho |
dc.contributor.author.fl_str_mv |
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 |
dc.subject.por.fl_str_mv |
Parkinson’s disease MPTP TUDCA Behavioral tests Neuroinflammation Ciências Médicas::Medicina Básica Science & Technology |
topic |
Parkinson’s disease MPTP TUDCA Behavioral tests Neuroinflammation Ciências Médicas::Medicina Básica Science & Technology |
description |
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. |
publishDate |
2018 |
dc.date.none.fl_str_mv |
2018-12 2018-12-01T00:00:00Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://hdl.handle.net/1822/57940 |
url |
http://hdl.handle.net/1822/57940 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
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, 1-17 0893-7648 1559-1182 10.1007/s12035-018-1062-4 29651747 https://link.springer.com/article/10.1007/s12035-018-1062-4 |
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info:eu-repo/semantics/openAccess |
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openAccess |
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application/pdf |
dc.publisher.none.fl_str_mv |
Springer |
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Springer |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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