Neuronal cytoskeletal dynamic modification induced by unconjugated bilirubin

Detalhes bibliográficos
Autor(a) principal: Coutinho, Eduarda Cristina Duarte de Magalhães
Data de Publicação: 2009
Tipo de documento: Dissertação
Idioma: eng
Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
Texto Completo: http://hdl.handle.net/10451/1804
Resumo: Tese de mestrado, Biologia (Biologia Molecular Humana), 2009, Universidade de Lisboa, Faculdade de Ciências
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spelling Neuronal cytoskeletal dynamic modification induced by unconjugated bilirubinNeurobiologiaHipocampoCitosqueletoTécnicas biológicasTeses de mestradoTese de mestrado, Biologia (Biologia Molecular Humana), 2009, Universidade de Lisboa, Faculdade de CiênciasHyperbilirubinemia is frequently observed in the neonatal period due to the transient accumulation of unconjugated bilirubin (UCB) in serum, which in certain circumstances it may trigger neurological deficits. We have recently shown that exposure of immature hippocampal neurons to UCB, in conditions mimicking moderate to severe neonatal jaundice, impairs neuronal development, with reduced neurogenesis, neurite arborization, and synaptogenesis. This project aimed to appraise the molecular mechanisms by which UCB may induce mild or severe alterations in the establishment of the normal neuronal architecture and inter-neurons communication that may ultimately elicit the appearance of neurological disabilities. As a first step to address this question we evaluated the effect of UCB at the neuronal cytoskeletal dynamics focusing on: (i) axonal elongation, (ii) microtubule polymerization and stabilization, and (iii) axonal transport. We first observed that UCB exposure lead to a higher percentage of neurons with decreased axonal length. Since microtubules polymerization and stability have crucial roles in axogenesis, we further investigated the polymerization rate of microtubules and found that it was also impaired after UCB exposure. In addition, hippocampal neurons treated with UCB revealed a more stable microtubules array, which may be related to a decreased axonal outgrowth. As our former results demonstrated that UCB increases microtubules stability, we decided to assess the UCB effects on microtubule associated proteins, MAP2 and Tau1. Curiously, we observed that UCB increases MAP2 axonal entry while it also enhances MAP2 and Tau1 expression along the axon, as well as their binding to microtubules. It is known that microtubule-bound Tau1 is able to interfere with the progress of motor proteins such as kinesin and dynein along the axon. Interestingly, in UCB-treated neurons we found a decreased expression of kinesin and a marked elevated expression of dynein, which may compromise the normal axonal transport. One of the cargoes transported via motor proteins are mitochondria. In this regard we demonstrated that UCB exposure induces mitochondria to aggregate and accumulate on the distal portion of the axon, suggesting a deficient axonal transport. These findings are new clues on the mechanisms of neurologic impairment induced by bilirubin in moderate to severe neonatal jaundice, showing cytoskeleton alterations similar to those often observed in neurological and neurodegenerative diseases.Resumo alargado em português disponível no documentoBrites, DoraMalhó, RuiRepositório da Universidade de LisboaCoutinho, Eduarda Cristina Duarte de Magalhães2010-07-28T16:13:16Z20092009-01-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesisapplication/pdfapplication/pdftext/xmlhttp://hdl.handle.net/10451/1804enghttp://catalogo.ul.pt/F/?func=item-global&doc_library=ULB01&type=03&doc_number=000576982info: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:RCAAP2023-11-08T15:41:47Zoai:repositorio.ul.pt:10451/1804Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T21:28:22.087632Repositório 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 Neuronal cytoskeletal dynamic modification induced by unconjugated bilirubin
title Neuronal cytoskeletal dynamic modification induced by unconjugated bilirubin
spellingShingle Neuronal cytoskeletal dynamic modification induced by unconjugated bilirubin
Coutinho, Eduarda Cristina Duarte de Magalhães
Neurobiologia
Hipocampo
Citosqueleto
Técnicas biológicas
Teses de mestrado
title_short Neuronal cytoskeletal dynamic modification induced by unconjugated bilirubin
title_full Neuronal cytoskeletal dynamic modification induced by unconjugated bilirubin
title_fullStr Neuronal cytoskeletal dynamic modification induced by unconjugated bilirubin
title_full_unstemmed Neuronal cytoskeletal dynamic modification induced by unconjugated bilirubin
title_sort Neuronal cytoskeletal dynamic modification induced by unconjugated bilirubin
author Coutinho, Eduarda Cristina Duarte de Magalhães
author_facet Coutinho, Eduarda Cristina Duarte de Magalhães
author_role author
dc.contributor.none.fl_str_mv Brites, Dora
Malhó, Rui
Repositório da Universidade de Lisboa
dc.contributor.author.fl_str_mv Coutinho, Eduarda Cristina Duarte de Magalhães
dc.subject.por.fl_str_mv Neurobiologia
Hipocampo
Citosqueleto
Técnicas biológicas
Teses de mestrado
topic Neurobiologia
Hipocampo
Citosqueleto
Técnicas biológicas
Teses de mestrado
description Tese de mestrado, Biologia (Biologia Molecular Humana), 2009, Universidade de Lisboa, Faculdade de Ciências
publishDate 2009
dc.date.none.fl_str_mv 2009
2009-01-01T00:00:00Z
2010-07-28T16:13:16Z
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/10451/1804
url http://hdl.handle.net/10451/1804
dc.language.iso.fl_str_mv eng
language eng
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dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
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dc.source.none.fl_str_mv reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
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instacron:RCAAP
instname_str Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
instacron_str RCAAP
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