Characterization of the striatal extracellular matrix in a mouse model of Parkinson’s disease

Detalhes bibliográficos
Autor(a) principal: Freitas, A
Data de Publicação: 2021
Outros Autores: Aroso, M, Barros, A, Fernández, M, Conde-Sousa, E, Leite, M, Carvalho, ED, Ribeiro, CC, Ferreira, R, Pêgo, AP, Vitorino, R, Gomez-Lazaro, M
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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spelling 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
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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
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