Neurotoxic effects of MPTP on mouse cerebral cortex: Modulation of neuroinflammation as a neuroprotective strategy
| Autor(a) principal: | |
|---|---|
| Data de Publicação: | 2019 |
| 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/10362/114756 |
Resumo: | POCI-01-0145-FEDER-007038. SFRH/BD/102771/2014 (to P.D.) and UMINHO/BI/248/2016 (to S.D.S.). This work has also been developed under the scope of the project NORTE-01-0145-FEDER000013, supported by the Northern Portugal Regional Operational Programme (NORTE 2020), under the Portugal 2020 Partnership Agreement, through the European Regional Development Fund (FEDER), and by FEDER funds, through the Competitiveness Factors Operational Programme (COMPETE). |
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Neurotoxic effects of MPTP on mouse cerebral cortex: Modulation of neuroinflammation as a neuroprotective strategyANXA1MicrogliaNeuroinflammationParkinson's diseaseTUDCAMolecular BiologyCellular and Molecular NeuroscienceCell BiologyPOCI-01-0145-FEDER-007038. SFRH/BD/102771/2014 (to P.D.) and UMINHO/BI/248/2016 (to S.D.S.). This work has also been developed under the scope of the project NORTE-01-0145-FEDER000013, supported by the Northern Portugal Regional Operational Programme (NORTE 2020), under the Portugal 2020 Partnership Agreement, through the European Regional Development Fund (FEDER), and by FEDER funds, through the Competitiveness Factors Operational Programme (COMPETE).Parkinson's disease (PD) is a progressive neurological disorder, mainly characterized by the progressive loss of dopaminergic neurons in the Substantia nigra pars compacta (SNpc) and by the presence of intracellular inclusions, known as Lewy bodies. Despite SNpc being considered the primary affected region in PD, the neuropathological features are confined solely to the nigro-striatal axis. With disease progression other brain regions are also affected, namely the cerebral cortex, although the spreading of the neurologic damage to this region is still not completely unraveled. Tauroursodeoxycholic acid (TUDCA) is an endogenous bile acid that has been shown to have antioxidant properties and to exhibit a neuroprotective effect in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mice model of PD. Moreover, TUDCA anti-inflammatory properties have been reported in glial cells, making it a prominent therapeutic agent in PD. Here, we used C57BL/6 mice injected with MPTP in a sub-acute paradigm aiming to investigate if the neurotoxic effects of MPTP could be extended to the cerebral cortex. In parallel, we evaluated the anti-oxidant, neuroprotective and anti-inflammatory effects of TUDCA. The anti-inflammatory mechanisms elicited by TUDCA were further dissected in microglia cells. Our results show that MPTP leads to a decrease of ATP and activated AMP-activated protein kinase levels in mice cortex, and to a transient increase in the expression of antioxidant downstream targets of nuclear factor erythroid 2 related factor 2 (Nrf-2), and parkin. Notably, MPTP increases pro-inflammatory markers, while down-regulating the expression of the anti-inflammatory protein Annexin-A1 (ANXA1). Importantly, we show that TUDCA treatment prevents the deleterious effects of MPTP, sustains increased levels of antioxidant enzymes and parkin, and most of all negatively modulates neuroinflammation and up-regulates ANXA1 expression. Additionally, results from cellular models using microglia corroborate TUDCA modulation of ANXA1 synthesis, linking inhibition of neuroinflammation and neuroprotection by TUDCA.DCV - Departamento de Ciências da VidaUCIBIO - Applied Molecular Biosciences UnitRUNMendes, Mariana OliveiraRosa, Alexandra IsabelCarvalho, Andreia NevesNunes, Maria JoãoDionísio, PedroRodrigues, ElsaCosta, DanielaDuarte-Silva, SaraMaciel, PatríciaRodrigues, Cecília Maria PereiraGama, Maria JoãoCastro-Caldas, Margarida2021-03-30T22:17:56Z2019-04-012019-04-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/article9application/pdfhttp://hdl.handle.net/10362/114756eng1044-7431PURE: 13269406https://doi.org/10.1016/j.mcn.2019.01.003info: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:RCAAP2024-03-11T04:57:31Zoai:run.unl.pt:10362/114756Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-20T03:42:37.764477Repositório 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 |
Neurotoxic effects of MPTP on mouse cerebral cortex: Modulation of neuroinflammation as a neuroprotective strategy |
| title |
Neurotoxic effects of MPTP on mouse cerebral cortex: Modulation of neuroinflammation as a neuroprotective strategy |
| spellingShingle |
Neurotoxic effects of MPTP on mouse cerebral cortex: Modulation of neuroinflammation as a neuroprotective strategy Mendes, Mariana Oliveira ANXA1 Microglia Neuroinflammation Parkinson's disease TUDCA Molecular Biology Cellular and Molecular Neuroscience Cell Biology |
| title_short |
Neurotoxic effects of MPTP on mouse cerebral cortex: Modulation of neuroinflammation as a neuroprotective strategy |
| title_full |
Neurotoxic effects of MPTP on mouse cerebral cortex: Modulation of neuroinflammation as a neuroprotective strategy |
| title_fullStr |
Neurotoxic effects of MPTP on mouse cerebral cortex: Modulation of neuroinflammation as a neuroprotective strategy |
| title_full_unstemmed |
Neurotoxic effects of MPTP on mouse cerebral cortex: Modulation of neuroinflammation as a neuroprotective strategy |
| title_sort |
Neurotoxic effects of MPTP on mouse cerebral cortex: Modulation of neuroinflammation as a neuroprotective strategy |
| author |
Mendes, Mariana Oliveira |
| author_facet |
Mendes, Mariana Oliveira Rosa, Alexandra Isabel Carvalho, Andreia Neves Nunes, Maria João Dionísio, Pedro Rodrigues, Elsa Costa, Daniela Duarte-Silva, Sara Maciel, Patrícia Rodrigues, Cecília Maria Pereira Gama, Maria João Castro-Caldas, Margarida |
| author_role |
author |
| author2 |
Rosa, Alexandra Isabel Carvalho, Andreia Neves Nunes, Maria João Dionísio, Pedro Rodrigues, Elsa Costa, Daniela Duarte-Silva, Sara Maciel, Patrícia Rodrigues, Cecília Maria Pereira Gama, Maria João Castro-Caldas, Margarida |
| author2_role |
author author author author author author author author author author author |
| dc.contributor.none.fl_str_mv |
DCV - Departamento de Ciências da Vida UCIBIO - Applied Molecular Biosciences Unit RUN |
| dc.contributor.author.fl_str_mv |
Mendes, Mariana Oliveira Rosa, Alexandra Isabel Carvalho, Andreia Neves Nunes, Maria João Dionísio, Pedro Rodrigues, Elsa Costa, Daniela Duarte-Silva, Sara Maciel, Patrícia Rodrigues, Cecília Maria Pereira Gama, Maria João Castro-Caldas, Margarida |
| dc.subject.por.fl_str_mv |
ANXA1 Microglia Neuroinflammation Parkinson's disease TUDCA Molecular Biology Cellular and Molecular Neuroscience Cell Biology |
| topic |
ANXA1 Microglia Neuroinflammation Parkinson's disease TUDCA Molecular Biology Cellular and Molecular Neuroscience Cell Biology |
| description |
POCI-01-0145-FEDER-007038. SFRH/BD/102771/2014 (to P.D.) and UMINHO/BI/248/2016 (to S.D.S.). This work has also been developed under the scope of the project NORTE-01-0145-FEDER000013, supported by the Northern Portugal Regional Operational Programme (NORTE 2020), under the Portugal 2020 Partnership Agreement, through the European Regional Development Fund (FEDER), and by FEDER funds, through the Competitiveness Factors Operational Programme (COMPETE). |
| publishDate |
2019 |
| dc.date.none.fl_str_mv |
2019-04-01 2019-04-01T00:00:00Z 2021-03-30T22:17:56Z |
| dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
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info:eu-repo/semantics/article |
| format |
article |
| status_str |
publishedVersion |
| dc.identifier.uri.fl_str_mv |
http://hdl.handle.net/10362/114756 |
| url |
http://hdl.handle.net/10362/114756 |
| dc.language.iso.fl_str_mv |
eng |
| language |
eng |
| dc.relation.none.fl_str_mv |
1044-7431 PURE: 13269406 https://doi.org/10.1016/j.mcn.2019.01.003 |
| dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
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openAccess |
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9 application/pdf |
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reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação instacron:RCAAP |
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Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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RCAAP |
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RCAAP |
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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) |
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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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