Exploring deregulated signals involved in motor neuron-microglia cross-talk in ALS

Detalhes bibliográficos
Autor(a) principal: Cunha, Maria Inês Fazendeiro
Data de Publicação: 2014
Tipo de documento: Dissertação
Idioma: eng
Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
Texto Completo: http://hdl.handle.net/10362/13873
Resumo: Part of the results discussed in this thesis was presented in the following meetings: Cunha MI, Cunha C, Vaz AR, Brites D. Studying microglial-motoneuron cross-talk in ALS pathology. 6th iMed.UL Postgraduate Students Meeting, Lisbon, July 2, 2014. [Abstract and Poster] Vaz AR. Motoneuron degeneration and glial reactivity in ALS: insights from cellular to animal models. Neuroscience Seminars at IMM 2012, Instituto de Medicina Molecular, Universidade de Lisboa, Lisbon, Portugal, June 9, 2014. [Oral Communication (by invitation)]
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spelling Exploring deregulated signals involved in motor neuron-microglia cross-talk in ALSMotor neuron dysfunctionNeuroinflammationMicroglia activation/deregulationMN-microglia cross-talkFractalkine -CX3CR1 axisHMGB1-TLRs signaling pathwaysPart of the results discussed in this thesis was presented in the following meetings: Cunha MI, Cunha C, Vaz AR, Brites D. Studying microglial-motoneuron cross-talk in ALS pathology. 6th iMed.UL Postgraduate Students Meeting, Lisbon, July 2, 2014. [Abstract and Poster] Vaz AR. Motoneuron degeneration and glial reactivity in ALS: insights from cellular to animal models. Neuroscience Seminars at IMM 2012, Instituto de Medicina Molecular, Universidade de Lisboa, Lisbon, Portugal, June 9, 2014. [Oral Communication (by invitation)]Amyotrophic Lateral Sclerosis (ALS) is the most common neurodegenerative disease affecting motor neurons (MNs). Neuroinflammation has shown to be a prominent pathological feature, highlighted by the presence of activated microglia, which may exert either beneficial or detrimental effects. Mutated MNs may release factors able to induce different microglial responses. However, how cells differently modulate each other remains elusive. Therefore, a better understanding of the MN-microglia signaling pathways compromised in ALS is warranted. Here, we aim (i) to uncover signaling pathways underlying MN injury and (ii) to dissect how MNs are modulating microglial response as well as the contribution of healthy microglia to rescue MN dysfunction. We focused on fractalkine-CX3XR1 axis, MFG-E8-mediated phagocytosis and HMGB1-TLR4 signaling. For this we used a MN-like cell line (NSC-34) stably transfected with human SOD1, either wild-type (wtMNs) or with G93A mutation (mMNs), alone or in mixed cultures with N9 microglial cell line. We observed a compromised viability of microglia in the presence of mMNs, yet they were more activated, as suggested by the increase of CD11b mRNA expression. The dysfunctional mechanisms associated with increased NO and decreased glutamate production by mMNs were not recovered by the presence of healthy microglia. However, the increased activity of matrix metalloproteinase -9 observed in mMNs was decreased in the presence of microglia. In addition, mMNs presented accumulation of membrane-fractalkine and, in mixed cultures, CX3CR1 mRNA expression was up-regulated in their presence. Furthermore, we showed that mMNs expressed higher levels of MFG-E8, which were further increased in the presence of microglia. Finally, both HMGB1 and TLR4 levels were also increased in mMNs, mainly in the presence of microglia. Together, these results highlight an impairment of microglial function caused by MN dysfunction and support the development of immunomodulatory strategies restoring both healthy state of microglia and MNs.Brites, DoraVaz, AnaRUNCunha, Maria Inês Fazendeiro2014-12-11T10:53:44Z2014-112014-122014-11-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesisapplication/pdfhttp://hdl.handle.net/10362/13873enginfo: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:RCAAP2024-03-11T03:48:45Zoai:run.unl.pt:10362/13873Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-20T03:21:28.617294Repositório 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 Exploring deregulated signals involved in motor neuron-microglia cross-talk in ALS
title Exploring deregulated signals involved in motor neuron-microglia cross-talk in ALS
spellingShingle Exploring deregulated signals involved in motor neuron-microglia cross-talk in ALS
Cunha, Maria Inês Fazendeiro
Motor neuron dysfunction
Neuroinflammation
Microglia activation/deregulation
MN-microglia cross-talk
Fractalkine -CX3CR1 axis
HMGB1-TLRs signaling pathways
title_short Exploring deregulated signals involved in motor neuron-microglia cross-talk in ALS
title_full Exploring deregulated signals involved in motor neuron-microglia cross-talk in ALS
title_fullStr Exploring deregulated signals involved in motor neuron-microglia cross-talk in ALS
title_full_unstemmed Exploring deregulated signals involved in motor neuron-microglia cross-talk in ALS
title_sort Exploring deregulated signals involved in motor neuron-microglia cross-talk in ALS
author Cunha, Maria Inês Fazendeiro
author_facet Cunha, Maria Inês Fazendeiro
author_role author
dc.contributor.none.fl_str_mv Brites, Dora
Vaz, Ana
RUN
dc.contributor.author.fl_str_mv Cunha, Maria Inês Fazendeiro
dc.subject.por.fl_str_mv Motor neuron dysfunction
Neuroinflammation
Microglia activation/deregulation
MN-microglia cross-talk
Fractalkine -CX3CR1 axis
HMGB1-TLRs signaling pathways
topic Motor neuron dysfunction
Neuroinflammation
Microglia activation/deregulation
MN-microglia cross-talk
Fractalkine -CX3CR1 axis
HMGB1-TLRs signaling pathways
description Part of the results discussed in this thesis was presented in the following meetings: Cunha MI, Cunha C, Vaz AR, Brites D. Studying microglial-motoneuron cross-talk in ALS pathology. 6th iMed.UL Postgraduate Students Meeting, Lisbon, July 2, 2014. [Abstract and Poster] Vaz AR. Motoneuron degeneration and glial reactivity in ALS: insights from cellular to animal models. Neuroscience Seminars at IMM 2012, Instituto de Medicina Molecular, Universidade de Lisboa, Lisbon, Portugal, June 9, 2014. [Oral Communication (by invitation)]
publishDate 2014
dc.date.none.fl_str_mv 2014-12-11T10:53:44Z
2014-11
2014-12
2014-11-01T00:00:00Z
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/10362/13873
url http://hdl.handle.net/10362/13873
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.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
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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
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