Dissecting neuronal development deficits by inflammation: from morphology to cytoskeleton dynamics

Detalhes bibliográficos
Autor(a) principal: Frias, Cátia Sofia Pereira
Data de Publicação: 2011
Tipo de documento: Dissertação
Idioma: eng
Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
Texto Completo: http://hdl.handle.net/10362/6710
Resumo: Dissertação para obtenção do Grau de Mestre em Genética Molecular e Biomedicina
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spelling Dissecting neuronal development deficits by inflammation: from morphology to cytoskeleton dynamicsNeuroinflammationHippocampal neuronsNeuronal arborizationGrowth coneSynaptogenesisCytoskeletonDissertação para obtenção do Grau de Mestre em Genética Molecular e BiomedicinaNeuroinflammation, a response of the nervous system to injury, results in the release of pro-inflammatory mediators, as interleukin-1β (IL-1β) and tumor necrosis factor-alpha (TNF-α). Exposure of nerve cells to a neuroinflammatory environment was shown to change the normal neurodevelopment, which can be linked to the appearance of neurological disabilities. In this work, we aimed to assess the effects of moderate levels of IL-1β and TNF-α in the establishment of neuronal arborization, growth cone morphology and synaptogenesis. An early exposure of embryonic hippocampal neurons to cytokines delay neuronal development, with an increase in the number of non-polarized cells, stage 2 of development. When analyzing stage 3 neurons, IL-1β showed to decrease total arborization, in particular at the axonal level, while TNF-α increased dendritic arborization. In fact, IL-1β reduces dendritic and axonal length and the number of axonal branches, whereas it increases the extent of dendritic and axonal branches, probably to compensate the other effects. In contrast, TNF-α increases the number of primary dendrites and dendritic branches, as well as their length. By next analyzing microtubule dynamics as the ratio of acetylated- (old) vs. tyrosinated-tubulin (newly-formed), we found that IL-1β and TNF-α induce microtubule stabilization, which may be related to a deficient axonal outgrowth. In addition, both cytokines reduced the area of growth cones, with an increase in the immunofluorescence of F-actin, indicating alterations at the cytoskeleton which may compromise axonal elongation and branching. Regarding neuronal connectivity, we demonstrated that both cytokines not only reduced the density of dendritic spines and synapses, but also the maturity of dendritic spines, suggesting a reduction in the synaptic strength. These findings establish a relation between neuroinflammation in fetal life and the emergence of neuronal damage, similar to those observed in neurodevelopmental disorders, as schizophrenia.FCT-UNLBrites, DoraBorralho, AdelaideRUNFrias, Cátia Sofia Pereira2012-01-12T12:01:50Z2011-122011-12-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesisapplication/pdfhttp://hdl.handle.net/10362/6710enginfo: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:RCAAP2024-03-11T03:37:55Zoai:run.unl.pt:10362/6710Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-20T03:16:57.606567Repositório 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 neuronal development deficits by inflammation: from morphology to cytoskeleton dynamics
title Dissecting neuronal development deficits by inflammation: from morphology to cytoskeleton dynamics
spellingShingle Dissecting neuronal development deficits by inflammation: from morphology to cytoskeleton dynamics
Frias, Cátia Sofia Pereira
Neuroinflammation
Hippocampal neurons
Neuronal arborization
Growth cone
Synaptogenesis
Cytoskeleton
title_short Dissecting neuronal development deficits by inflammation: from morphology to cytoskeleton dynamics
title_full Dissecting neuronal development deficits by inflammation: from morphology to cytoskeleton dynamics
title_fullStr Dissecting neuronal development deficits by inflammation: from morphology to cytoskeleton dynamics
title_full_unstemmed Dissecting neuronal development deficits by inflammation: from morphology to cytoskeleton dynamics
title_sort Dissecting neuronal development deficits by inflammation: from morphology to cytoskeleton dynamics
author Frias, Cátia Sofia Pereira
author_facet Frias, Cátia Sofia Pereira
author_role author
dc.contributor.none.fl_str_mv Brites, Dora
Borralho, Adelaide
RUN
dc.contributor.author.fl_str_mv Frias, Cátia Sofia Pereira
dc.subject.por.fl_str_mv Neuroinflammation
Hippocampal neurons
Neuronal arborization
Growth cone
Synaptogenesis
Cytoskeleton
topic Neuroinflammation
Hippocampal neurons
Neuronal arborization
Growth cone
Synaptogenesis
Cytoskeleton
description Dissertação para obtenção do Grau de Mestre em Genética Molecular e Biomedicina
publishDate 2011
dc.date.none.fl_str_mv 2011-12
2011-12-01T00:00:00Z
2012-01-12T12:01:50Z
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/10362/6710
url http://hdl.handle.net/10362/6710
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 FCT-UNL
publisher.none.fl_str_mv FCT-UNL
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
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