Characterization of the striatal extracellular matrix in a mouse model of Parkinson’s disease
Autor(a) principal: | |
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Data de Publicação: | 2021 |
Outros Autores: | , , , , , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
Texto Completo: | https://hdl.handle.net/10216/153745 |
Resumo: | Parkinson’s disease’s etiology is unknown, although evidence suggests the involvement of oxidative modifications of intracellular components in disease pathobiology. Despite the known involvement of the extracellular matrix in physiology and disease, the influence of oxidative stress on the matrix has been neglected. The chemical modifications that might accumulate in matrix components due to their long half-live and the low amount of extracellular antioxidants could also contribute to the disease and explain ineffective cellular therapies. The enriched striatal extracellular matrix from a mouse model of Parkinson’s disease was characterized by Raman spectroscopy. We found a matrix fingerprint of increased oxalate content and oxidative modifications. To uncover the effects of these changes on brain cells, we morphologically characterized the primary microglia used to repopulate this matrix and further quantified the effects on cellular mechanical stress by an intracellular fluorescence resonance energy transfer (FRET)-mechanosensor using the U-2 OS cell line. Our data suggest changes in microglia survival and morphology, and a decrease in cytoskeletal tension in response to the modified matrix from both hemispheres of 6-hydroxydopamine (6-OHDA)-lesioned animals. Collectively, these data suggest that the extracellular matrix is modified, and underscore the need for its thorough investigation, which may reveal new ways to improve therapies or may even reveal new therapies. |
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Characterization of the striatal extracellular matrix in a mouse model of Parkinson’s diseaseExtracellular matrixOxidative stressParkinson’s diseaseRaman spectroscopyParkinson’s disease’s etiology is unknown, although evidence suggests the involvement of oxidative modifications of intracellular components in disease pathobiology. Despite the known involvement of the extracellular matrix in physiology and disease, the influence of oxidative stress on the matrix has been neglected. The chemical modifications that might accumulate in matrix components due to their long half-live and the low amount of extracellular antioxidants could also contribute to the disease and explain ineffective cellular therapies. The enriched striatal extracellular matrix from a mouse model of Parkinson’s disease was characterized by Raman spectroscopy. We found a matrix fingerprint of increased oxalate content and oxidative modifications. To uncover the effects of these changes on brain cells, we morphologically characterized the primary microglia used to repopulate this matrix and further quantified the effects on cellular mechanical stress by an intracellular fluorescence resonance energy transfer (FRET)-mechanosensor using the U-2 OS cell line. Our data suggest changes in microglia survival and morphology, and a decrease in cytoskeletal tension in response to the modified matrix from both hemispheres of 6-hydroxydopamine (6-OHDA)-lesioned animals. Collectively, these data suggest that the extracellular matrix is modified, and underscore the need for its thorough investigation, which may reveal new ways to improve therapies or may even reveal new therapies.MDPI20212021-01-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttps://hdl.handle.net/10216/153745eng2076-392110.3390/antiox10071095Freitas, AAroso, MBarros, AFernández, MConde-Sousa, ELeite, MCarvalho, EDRibeiro, CCFerreira, RPêgo, APVitorino, RGomez-Lazaro, Minfo: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:RCAAP2023-11-29T14:11:25Zoai:repositorio-aberto.up.pt:10216/153745Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T23:56:41.607011Repositório 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 |
Characterization of the striatal extracellular matrix in a mouse model of Parkinson’s disease |
title |
Characterization of the striatal extracellular matrix in a mouse model of Parkinson’s disease |
spellingShingle |
Characterization of the striatal extracellular matrix in a mouse model of Parkinson’s disease Freitas, A Extracellular matrix Oxidative stress Parkinson’s disease Raman spectroscopy |
title_short |
Characterization of the striatal extracellular matrix in a mouse model of Parkinson’s disease |
title_full |
Characterization of the striatal extracellular matrix in a mouse model of Parkinson’s disease |
title_fullStr |
Characterization of the striatal extracellular matrix in a mouse model of Parkinson’s disease |
title_full_unstemmed |
Characterization of the striatal extracellular matrix in a mouse model of Parkinson’s disease |
title_sort |
Characterization of the striatal extracellular matrix in a mouse model of Parkinson’s disease |
author |
Freitas, A |
author_facet |
Freitas, A Aroso, M Barros, A Fernández, M Conde-Sousa, E Leite, M Carvalho, ED Ribeiro, CC Ferreira, R Pêgo, AP Vitorino, R Gomez-Lazaro, M |
author_role |
author |
author2 |
Aroso, M Barros, A Fernández, M Conde-Sousa, E Leite, M Carvalho, ED Ribeiro, CC Ferreira, R Pêgo, AP Vitorino, R Gomez-Lazaro, M |
author2_role |
author author author author author author author author author author author |
dc.contributor.author.fl_str_mv |
Freitas, A Aroso, M Barros, A Fernández, M Conde-Sousa, E Leite, M Carvalho, ED Ribeiro, CC Ferreira, R Pêgo, AP Vitorino, R Gomez-Lazaro, M |
dc.subject.por.fl_str_mv |
Extracellular matrix Oxidative stress Parkinson’s disease Raman spectroscopy |
topic |
Extracellular matrix Oxidative stress Parkinson’s disease Raman spectroscopy |
description |
Parkinson’s disease’s etiology is unknown, although evidence suggests the involvement of oxidative modifications of intracellular components in disease pathobiology. Despite the known involvement of the extracellular matrix in physiology and disease, the influence of oxidative stress on the matrix has been neglected. The chemical modifications that might accumulate in matrix components due to their long half-live and the low amount of extracellular antioxidants could also contribute to the disease and explain ineffective cellular therapies. The enriched striatal extracellular matrix from a mouse model of Parkinson’s disease was characterized by Raman spectroscopy. We found a matrix fingerprint of increased oxalate content and oxidative modifications. To uncover the effects of these changes on brain cells, we morphologically characterized the primary microglia used to repopulate this matrix and further quantified the effects on cellular mechanical stress by an intracellular fluorescence resonance energy transfer (FRET)-mechanosensor using the U-2 OS cell line. Our data suggest changes in microglia survival and morphology, and a decrease in cytoskeletal tension in response to the modified matrix from both hemispheres of 6-hydroxydopamine (6-OHDA)-lesioned animals. Collectively, these data suggest that the extracellular matrix is modified, and underscore the need for its thorough investigation, which may reveal new ways to improve therapies or may even reveal new therapies. |
publishDate |
2021 |
dc.date.none.fl_str_mv |
2021 2021-01-01T00:00:00Z |
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 |
https://hdl.handle.net/10216/153745 |
url |
https://hdl.handle.net/10216/153745 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
2076-3921 10.3390/antiox10071095 |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
application/pdf |
dc.publisher.none.fl_str_mv |
MDPI |
publisher.none.fl_str_mv |
MDPI |
dc.source.none.fl_str_mv |
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 |
reponame_str |
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 |
repository.mail.fl_str_mv |
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1799135887371534336 |