Dissecting neuronal development deficits by inflammation: from morphology to cytoskeleton dynamics
Autor(a) principal: | |
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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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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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7160 |
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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 |
|
_version_ |
1799137818590576640 |