Dissecting cross-talk between microglia and motoneurons in ALS: signaling events and soluble factors

Detalhes bibliográficos
Autor(a) principal: Barbosa, Marta Isabel da Silva Rodrigues
Data de Publicação: 2013
Tipo de documento: Dissertação
Idioma: eng
Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
Texto Completo: http://hdl.handle.net/10362/10925
Resumo: Dissertação para obtenção do Grau de Mestre em Genética Molecular e Biomedicina
id RCAP_3c70709b3c8541b34a4dbcc68575cb44
oai_identifier_str oai:run.unl.pt:10362/10925
network_acronym_str RCAP
network_name_str Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
repository_id_str 7160
spelling Dissecting cross-talk between microglia and motoneurons in ALS: signaling events and soluble factorsInflammatory mediatorsMicroglia modulatory effects of motoneuron degenerationMicroglia-motoneuron communicationNeuroinflammationSOD1 accumulationDissertação para obtenção do Grau de Mestre em Genética Molecular e BiomedicinaConvergence of pathways in motoneuron (MN) injury include microglia in the initiation and progression of Amyotrophic Lateral Sclerosis (ALS). Neuroinflammation is a pathological hallmark of ALS and microglia may acquire neurotoxic or neuroprotective properties in response to misfolded superoxide dismutase-1 (SOD1) or other molecules produced by the injured MN. We assessed: (i) the role of microglia in preventing/restoring MN dysfunction using a mixed culture of NSC-34 MN-like cells (mutated in G93A) and of N9 microglia cells, added at 0 or 2 days-invitro(M0, M2) and cultured till 4 and 7 days-in-vitro; (ii) neurodegenerative network in organotypic cultures from lumbar segments of spinal cord (SC) obtained from the ALS mice model TgSOD1-G93A at 7 day-old and aged for 10 days-in-vitro, as well as the response to lipopolysaccharide (LPS, 1μg/mL) immunostimulation. Western blot assays for SOD1, high-mobility-group-box-protein-1 (HMGB1) and toll-like receptor-4 (TLR-4), and fluorimetric/colorimetric assays for ATP, glutamate and nitric oxide (NO), were used. Microglia (M0/M2) decreased the accumulation of human/mouse mutated SOD1 (P<0.01). In addition, elevation of glutamate efflux (P<0.01), and reduction of extracellular ATP (P<0.01), MMP-2(P<0.05) and MMP-9 (P<0.01) was observed by M2 at 7 days-in-vitro. Reduction of NO (P<0.05) and MMP-2 (P<0.01) was obtained with M0. HMGB1 increased by M0 and decreased by M2, suggesting HMGB1 release from the cell. Accumulation of SOD1 was verified in SC organotypic cultures, but no changes in ATP or NO were obtained, although a slight decrease in ATP by LPS was verified. Downregulation of TLR-4 by LPS may indicate the exhaustion of the inflammatory response mechanisms in the aged SC culture. Together, these results suggest that microglia by inhibiting MMP activation and HMGB1 cytoplasmic translocation in the ALS model are key in modulating MN degeneration and should be considered as therapeutic targets in ALS.supported by FEDER (COMPETE Programme) and by National funds (Fundação para a Ciência e a Tecnologia – FCT, Portugal) with the projects PTDC/SAU-FAR/118787/2010 to D.B. and PEst-OE/SAU/UI4013/2011 and 2012 to iMed.ULFaculdade de Ciências e TecnologiaBrites, DoraVaz, AnaRUNBarbosa, Marta Isabel da Silva Rodrigues2014-01-02T17:17:35Z20132013-01-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesisapplication/pdfhttp://hdl.handle.net/10362/10925enginfo: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:RCAAP2024-03-11T03:45:01Zoai:run.unl.pt:10362/10925Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-20T03:19:51.504682Repositório 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 Dissecting cross-talk between microglia and motoneurons in ALS: signaling events and soluble factors
title Dissecting cross-talk between microglia and motoneurons in ALS: signaling events and soluble factors
spellingShingle Dissecting cross-talk between microglia and motoneurons in ALS: signaling events and soluble factors
Barbosa, Marta Isabel da Silva Rodrigues
Inflammatory mediators
Microglia modulatory effects of motoneuron degeneration
Microglia-motoneuron communication
Neuroinflammation
SOD1 accumulation
title_short Dissecting cross-talk between microglia and motoneurons in ALS: signaling events and soluble factors
title_full Dissecting cross-talk between microglia and motoneurons in ALS: signaling events and soluble factors
title_fullStr Dissecting cross-talk between microglia and motoneurons in ALS: signaling events and soluble factors
title_full_unstemmed Dissecting cross-talk between microglia and motoneurons in ALS: signaling events and soluble factors
title_sort Dissecting cross-talk between microglia and motoneurons in ALS: signaling events and soluble factors
author Barbosa, Marta Isabel da Silva Rodrigues
author_facet Barbosa, Marta Isabel da Silva Rodrigues
author_role author
dc.contributor.none.fl_str_mv Brites, Dora
Vaz, Ana
RUN
dc.contributor.author.fl_str_mv Barbosa, Marta Isabel da Silva Rodrigues
dc.subject.por.fl_str_mv Inflammatory mediators
Microglia modulatory effects of motoneuron degeneration
Microglia-motoneuron communication
Neuroinflammation
SOD1 accumulation
topic Inflammatory mediators
Microglia modulatory effects of motoneuron degeneration
Microglia-motoneuron communication
Neuroinflammation
SOD1 accumulation
description Dissertação para obtenção do Grau de Mestre em Genética Molecular e Biomedicina
publishDate 2013
dc.date.none.fl_str_mv 2013
2013-01-01T00:00:00Z
2014-01-02T17:17:35Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/masterThesis
format masterThesis
status_str publishedVersion
dc.identifier.uri.fl_str_mv http://hdl.handle.net/10362/10925
url http://hdl.handle.net/10362/10925
dc.language.iso.fl_str_mv eng
language eng
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 Faculdade de Ciências e Tecnologia
publisher.none.fl_str_mv Faculdade de Ciências e Tecnologia
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
instname_str Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
instacron_str RCAAP
institution RCAAP
reponame_str Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
collection Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
repository.name.fl_str_mv 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
_version_ 1799137841448484864

Registros relacionados