Ex vivo model of epilepsy in organotypic slices : a new tool for drug screening
| Autor(a) principal: | |
|---|---|
| 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/10451/49581 |
Resumo: | © The Author(s). 2018 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated |
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Ex vivo model of epilepsy in organotypic slices : a new tool for drug screeningEpilepsyGliosisInterleukin-1βNLRP3 inflammasomeNeuroinflammationOrganotypic slice culturesProinflammatory cytokines© The Author(s). 2018 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise statedBackground: Epilepsy is a prevalent neurological disorder worldwide. It is characterized by an enduring predisposition to generate seizures and its development is accompanied by alterations in many cellular processes. Organotypic slice cultures represent a multicellular environment with the potential to assess biological mechanisms, and they are used as a starting point for refining molecules for in vivo studies. Here, we investigated organotypic slice cultures as a model of epilepsy. Methods: We assessed, by electrophysiological recordings, the spontaneous activity of organotypic slices maintained under different culture protocols. Moreover, we evaluated, through molecular-based approaches, neurogenesis, neuronal death, gliosis, expression of proinflammatory cytokines, and activation of NLRP3 inflammasome (nucleotide-binding, leucine-rich repeat, pyrin domain) as biomarkers of neuroinflammation. Results: We demonstrated that organotypic slices, maintained under a serum deprivation culture protocol, develop epileptic-like activity. Furthermore, throughout a comparative study with slices that do not depict any epileptiform activity, slices with epileptiform activity were found to display significant differences in terms of inflammation-related features, such as (1) increased neuronal death, with higher incidence in CA1 pyramidal neurons of the hippocampus; (2) activation of astrocytes and microglia, assessed through western blot and immunohistochemistry; (3) upregulation of proinflammatory cytokines, specifically interleukin-1β (IL-1β), interleukin-6, and tumor necrosis factor α, revealed by qPCR; and (4) enhanced expression of NLRP3, assessed by western blot, together with increased NLRP3 activation, showed by IL-1β quantification. Conclusions: Thus, organotypic slice cultures gradually deprived of serum mimic the epileptic-like activity, as well as the inflammatory events associated with in vivo epilepsy. This system can be considered a new tool to explore the interplay between neuroinflammation and epilepsy and to screen potential drug candidates, within the inflammatory cascades, to reduce/halt epileptogenesis.The funding reference is LISBOA-01-0145-FEDER-007391, and the project was cofunded by FEDER, through POR Lisboa 2020–Programa Operacional Regional de Lisboa, PORTUGAL 2020, and Fundação para a Ciência e a Tecnologia. Diogo M. Rombo was in receipt of a fellowship from Fundação para a Ciência e a Tecnologia, SFRH/BD/60386/2009.Springer NatureRepositório da Universidade de LisboaMagalhães, DanielaPereira, NoémiaRombo, Diogo M.Beltrão-Cavacas, CláudiaSebastião, Ana MValente, Cláudia A.2021-09-22T17:19:59Z20182018-01-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10451/49581engJ Neuroinflammation. 2018 Jul 11;15(1):20310.1186/s12974-018-1225-21742-2094info: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:RCAAP2023-11-08T16:53:29Zoai:repositorio.ul.pt:10451/49581Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T22:01:12.807470Repositório 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 |
Ex vivo model of epilepsy in organotypic slices : a new tool for drug screening |
| title |
Ex vivo model of epilepsy in organotypic slices : a new tool for drug screening |
| spellingShingle |
Ex vivo model of epilepsy in organotypic slices : a new tool for drug screening Magalhães, Daniela Epilepsy Gliosis Interleukin-1β NLRP3 inflammasome Neuroinflammation Organotypic slice cultures Proinflammatory cytokines |
| title_short |
Ex vivo model of epilepsy in organotypic slices : a new tool for drug screening |
| title_full |
Ex vivo model of epilepsy in organotypic slices : a new tool for drug screening |
| title_fullStr |
Ex vivo model of epilepsy in organotypic slices : a new tool for drug screening |
| title_full_unstemmed |
Ex vivo model of epilepsy in organotypic slices : a new tool for drug screening |
| title_sort |
Ex vivo model of epilepsy in organotypic slices : a new tool for drug screening |
| author |
Magalhães, Daniela |
| author_facet |
Magalhães, Daniela Pereira, Noémia Rombo, Diogo M. Beltrão-Cavacas, Cláudia Sebastião, Ana M Valente, Cláudia A. |
| author_role |
author |
| author2 |
Pereira, Noémia Rombo, Diogo M. Beltrão-Cavacas, Cláudia Sebastião, Ana M Valente, Cláudia A. |
| author2_role |
author author author author author |
| dc.contributor.none.fl_str_mv |
Repositório da Universidade de Lisboa |
| dc.contributor.author.fl_str_mv |
Magalhães, Daniela Pereira, Noémia Rombo, Diogo M. Beltrão-Cavacas, Cláudia Sebastião, Ana M Valente, Cláudia A. |
| dc.subject.por.fl_str_mv |
Epilepsy Gliosis Interleukin-1β NLRP3 inflammasome Neuroinflammation Organotypic slice cultures Proinflammatory cytokines |
| topic |
Epilepsy Gliosis Interleukin-1β NLRP3 inflammasome Neuroinflammation Organotypic slice cultures Proinflammatory cytokines |
| description |
© The Author(s). 2018 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated |
| publishDate |
2018 |
| dc.date.none.fl_str_mv |
2018 2018-01-01T00:00:00Z 2021-09-22T17:19:59Z |
| 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/10451/49581 |
| url |
http://hdl.handle.net/10451/49581 |
| dc.language.iso.fl_str_mv |
eng |
| language |
eng |
| dc.relation.none.fl_str_mv |
J Neuroinflammation. 2018 Jul 11;15(1):203 10.1186/s12974-018-1225-2 1742-2094 |
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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 Nature |
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Springer Nature |
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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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