Ácido quinolínico e neurodegeneração glutamatérgia em Caenorhabditis elegans
Autor(a) principal: | |
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Data de Publicação: | 2019 |
Tipo de documento: | Dissertação |
Idioma: | por |
Título da fonte: | Biblioteca Digital de Teses e Dissertações do UFSM |
Texto Completo: | http://repositorio.ufsm.br/handle/1/19176 |
Resumo: | Quinolinic acid (QUIN) is an endogenous neurotoxin that acts as an N-methyl-D-aspartate receptor (NMDAR) agonist generating a toxic cascade, which can lead to neurodegeneration. The action of QUIN in Caenorhabditis elegans and the neurotoxins that allows the study of glutamatergic system disorders have not been carefully addressed. The effects of QUIN on toxicological and behavioral parameters in VM487 (nmr-1) and VC2623 (nmr-2) mutants strains, as well as in wild-type (WT) animals were performed to evaluate whether QUIN could be used as a neurotoxin in C. elegans. QUIN reduced survival of WT worms in a dose-dependent manner. A sublethal concentration of QUIN (20 mM) increased reactive oxygen species (ROS) levels in a nmr-1/NMDAR-dependent manner, activated the DAF-16/FOXO transcription factor, and increased expression of the proteins, as the superoxide dismutase-3, Glutathione S-transferase-4, and heat shock protein-16.2. QUIN did not change motor behavioral parameters but altered the sensory behavior in WT and VM487 (nmr-1) worms. Notably, the effect of QUIN on the sensory behavioral parameters might occur, at least in part, secondary to increased ROS. However, the touch response behavior indicates a mechanism of action independent of ROS generation. In addition, the non-lethal concentration of QUIN can have unleashed possible neurodegeneration in the glutamatergic system considering the relation between the behavioral data and the GFP-neuronal measures. Our findings indicate that C. elegans have a QUIN mechanism like that found in organisms like mammals, indicating that it can be useful to studies with the glutamatergic system. Thus, the C. elegans can be used more specifically in diseases that have among their etiologies the glutamatergic excitotoxicity as in mammals. |
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2019-12-18T13:43:39Z2019-12-18T13:43:39Z2019-07-26http://repositorio.ufsm.br/handle/1/19176Quinolinic acid (QUIN) is an endogenous neurotoxin that acts as an N-methyl-D-aspartate receptor (NMDAR) agonist generating a toxic cascade, which can lead to neurodegeneration. The action of QUIN in Caenorhabditis elegans and the neurotoxins that allows the study of glutamatergic system disorders have not been carefully addressed. The effects of QUIN on toxicological and behavioral parameters in VM487 (nmr-1) and VC2623 (nmr-2) mutants strains, as well as in wild-type (WT) animals were performed to evaluate whether QUIN could be used as a neurotoxin in C. elegans. QUIN reduced survival of WT worms in a dose-dependent manner. A sublethal concentration of QUIN (20 mM) increased reactive oxygen species (ROS) levels in a nmr-1/NMDAR-dependent manner, activated the DAF-16/FOXO transcription factor, and increased expression of the proteins, as the superoxide dismutase-3, Glutathione S-transferase-4, and heat shock protein-16.2. QUIN did not change motor behavioral parameters but altered the sensory behavior in WT and VM487 (nmr-1) worms. Notably, the effect of QUIN on the sensory behavioral parameters might occur, at least in part, secondary to increased ROS. However, the touch response behavior indicates a mechanism of action independent of ROS generation. In addition, the non-lethal concentration of QUIN can have unleashed possible neurodegeneration in the glutamatergic system considering the relation between the behavioral data and the GFP-neuronal measures. Our findings indicate that C. elegans have a QUIN mechanism like that found in organisms like mammals, indicating that it can be useful to studies with the glutamatergic system. Thus, the C. elegans can be used more specifically in diseases that have among their etiologies the glutamatergic excitotoxicity as in mammals.O ácido quinolínico (QUIN) é uma neurotoxina endógena que atua como agonista do receptor N-metil-D-aspartato (NMDAR) gerando uma cascata tóxica, que pode levar à neurodegeneração. A ação de QUIN em Caenorhabditis elegans, bem como de outras neurotoxinas que permitem o estudo dos distúrbios do sistema glutamatérgico, ainda não foram totalmente elucidadas. Os efeitos de QUIN em parâmetros toxicológicos e comportamentais em animais mutantes VM487 (nmr-1) e VC2623 (nmr-2) e selvagem Bristol N2 (WT) foram realizados para avaliar se QUIN poderia ser usado como uma neurotoxina em C. elegans. O QUIN reduziu a sobrevivência de vermes WT de uma forma dose dependente. Uma concentração não letal de QUIN (20 mM) aumentou os níveis de espécies reativas de oxigênio (ROS) de uma maneira dependente de NMR-1/NMDAR, ativou o fator de transcrição DAF-16/FOXO e aumentou a expressão de proteínas como a superóxido dismutase-3, Glutationa S-transferase-4 e a proteína de choque térmico-16.2. O QUIN não alterou os parâmetros comportamentais motores, mas alterou o comportamento sensorial em animais WT e VM487 (nmr-1). Notavelmente, o efeito de QUIN nos parâmetros comportamentais sensoriais pode ocorrer, pelo menos em parte, secundário ao aumento de ROS. No entanto, o comportamento de resposta ao toque indica um mecanismo de ação que pode ser independente da geração de ROS diretamente. Além disso, doses não letais de QUIN podem ter desencadeado uma possível neurodegeneração no sistema glutamatérgicos considerando a relação entre os dados comportamentais e as medidas de GFP-neuronal. Nossos achados indicam que o C. elegans tem um mecanismo de ação do QUIN similar ao que encontramos em organismos como os mamíferos, o que indica que o modelo alternativo pode ser útil para estudos com o sistema glutamatérgico. Assim, o C. elegans pode ser usado mais especificamente em doenças que possam ter entre suas etiologias a excitotoxicidade glutamatérgica assim como em mamíferos.Conselho Nacional de Pesquisa e Desenvolvimento Científico e Tecnológico - CNPqporUniversidade Federal de Santa MariaCentro de Ciências Naturais e ExatasPrograma de Pós-Graduação em Ciências Biológicas: Bioquímica ToxicológicaUFSMBrasilBioquímicaAttribution-NonCommercial-NoDerivatives 4.0 Internationalhttp://creativecommons.org/licenses/by-nc-nd/4.0/info:eu-repo/semantics/openAccessNeurotransmissão glutamatérgicaNeurodegeneraçãoNMDAQUINExcitotoxicidadeGlutamatergic neurotransmissionNeurodegenerationExcitotoxicityCNPQ::CIENCIAS BIOLOGICAS::BIOQUIMICAÁcido quinolínico e neurodegeneração glutamatérgia em Caenorhabditis elegansQuinolinic acid and glutamatergic neurodegeneration in Caenorhabditis elegansinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesisSoares, Félix Alexandre Antuneshttp://lattes.cnpq.br/8752453650114092Ávila, Daiana Silva dehttp://lattes.cnpq.br/4355211015887363Loreto, Elgion Lucio da Silvahttp://lattes.cnpq.br/6493669115018157http://lattes.cnpq.br/6456013124625476Silveira, Tássia Limana da2008000000026003aef53b7-b173-4c56-a944-bed2de5e5ddaa01f7107-12d1-4f23-8f02-e62613b1121e9f9969d1-7d48-45fd-9ea7-9a55acc6fc28ab41f5b8-3dea-4caa-86ab-c37a1044a379reponame:Biblioteca Digital de Teses e Dissertações do UFSMinstname:Universidade Federal de Santa Maria (UFSM)instacron:UFSMORIGINALDIS_PPGCBBT_2019_SILVEIRA_TASSIA.pdfDIS_PPGCBBT_2019_SILVEIRA_TASSIA.pdfDissertação de Mestradoapplication/pdf4566553http://repositorio.ufsm.br/bitstream/1/19176/1/DIS_PPGCBBT_2019_SILVEIRA_TASSIA.pdff32297cd74f362e0c3d75f94fc479132MD51CC-LICENSElicense_rdflicense_rdfapplication/rdf+xml; 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dc.title.por.fl_str_mv |
Ácido quinolínico e neurodegeneração glutamatérgia em Caenorhabditis elegans |
dc.title.alternative.eng.fl_str_mv |
Quinolinic acid and glutamatergic neurodegeneration in Caenorhabditis elegans |
title |
Ácido quinolínico e neurodegeneração glutamatérgia em Caenorhabditis elegans |
spellingShingle |
Ácido quinolínico e neurodegeneração glutamatérgia em Caenorhabditis elegans Silveira, Tássia Limana da Neurotransmissão glutamatérgica Neurodegeneração NMDA QUIN Excitotoxicidade Glutamatergic neurotransmission Neurodegeneration Excitotoxicity CNPQ::CIENCIAS BIOLOGICAS::BIOQUIMICA |
title_short |
Ácido quinolínico e neurodegeneração glutamatérgia em Caenorhabditis elegans |
title_full |
Ácido quinolínico e neurodegeneração glutamatérgia em Caenorhabditis elegans |
title_fullStr |
Ácido quinolínico e neurodegeneração glutamatérgia em Caenorhabditis elegans |
title_full_unstemmed |
Ácido quinolínico e neurodegeneração glutamatérgia em Caenorhabditis elegans |
title_sort |
Ácido quinolínico e neurodegeneração glutamatérgia em Caenorhabditis elegans |
author |
Silveira, Tássia Limana da |
author_facet |
Silveira, Tássia Limana da |
author_role |
author |
dc.contributor.advisor1.fl_str_mv |
Soares, Félix Alexandre Antunes |
dc.contributor.advisor1Lattes.fl_str_mv |
http://lattes.cnpq.br/8752453650114092 |
dc.contributor.referee1.fl_str_mv |
Ávila, Daiana Silva de |
dc.contributor.referee1Lattes.fl_str_mv |
http://lattes.cnpq.br/4355211015887363 |
dc.contributor.referee2.fl_str_mv |
Loreto, Elgion Lucio da Silva |
dc.contributor.referee2Lattes.fl_str_mv |
http://lattes.cnpq.br/6493669115018157 |
dc.contributor.authorLattes.fl_str_mv |
http://lattes.cnpq.br/6456013124625476 |
dc.contributor.author.fl_str_mv |
Silveira, Tássia Limana da |
contributor_str_mv |
Soares, Félix Alexandre Antunes Ávila, Daiana Silva de Loreto, Elgion Lucio da Silva |
dc.subject.por.fl_str_mv |
Neurotransmissão glutamatérgica Neurodegeneração NMDA QUIN Excitotoxicidade |
topic |
Neurotransmissão glutamatérgica Neurodegeneração NMDA QUIN Excitotoxicidade Glutamatergic neurotransmission Neurodegeneration Excitotoxicity CNPQ::CIENCIAS BIOLOGICAS::BIOQUIMICA |
dc.subject.eng.fl_str_mv |
Glutamatergic neurotransmission Neurodegeneration Excitotoxicity |
dc.subject.cnpq.fl_str_mv |
CNPQ::CIENCIAS BIOLOGICAS::BIOQUIMICA |
description |
Quinolinic acid (QUIN) is an endogenous neurotoxin that acts as an N-methyl-D-aspartate receptor (NMDAR) agonist generating a toxic cascade, which can lead to neurodegeneration. The action of QUIN in Caenorhabditis elegans and the neurotoxins that allows the study of glutamatergic system disorders have not been carefully addressed. The effects of QUIN on toxicological and behavioral parameters in VM487 (nmr-1) and VC2623 (nmr-2) mutants strains, as well as in wild-type (WT) animals were performed to evaluate whether QUIN could be used as a neurotoxin in C. elegans. QUIN reduced survival of WT worms in a dose-dependent manner. A sublethal concentration of QUIN (20 mM) increased reactive oxygen species (ROS) levels in a nmr-1/NMDAR-dependent manner, activated the DAF-16/FOXO transcription factor, and increased expression of the proteins, as the superoxide dismutase-3, Glutathione S-transferase-4, and heat shock protein-16.2. QUIN did not change motor behavioral parameters but altered the sensory behavior in WT and VM487 (nmr-1) worms. Notably, the effect of QUIN on the sensory behavioral parameters might occur, at least in part, secondary to increased ROS. However, the touch response behavior indicates a mechanism of action independent of ROS generation. In addition, the non-lethal concentration of QUIN can have unleashed possible neurodegeneration in the glutamatergic system considering the relation between the behavioral data and the GFP-neuronal measures. Our findings indicate that C. elegans have a QUIN mechanism like that found in organisms like mammals, indicating that it can be useful to studies with the glutamatergic system. Thus, the C. elegans can be used more specifically in diseases that have among their etiologies the glutamatergic excitotoxicity as in mammals. |
publishDate |
2019 |
dc.date.accessioned.fl_str_mv |
2019-12-18T13:43:39Z |
dc.date.available.fl_str_mv |
2019-12-18T13:43:39Z |
dc.date.issued.fl_str_mv |
2019-07-26 |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/masterThesis |
format |
masterThesis |
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publishedVersion |
dc.identifier.uri.fl_str_mv |
http://repositorio.ufsm.br/handle/1/19176 |
url |
http://repositorio.ufsm.br/handle/1/19176 |
dc.language.iso.fl_str_mv |
por |
language |
por |
dc.relation.cnpq.fl_str_mv |
200800000002 |
dc.relation.confidence.fl_str_mv |
600 |
dc.relation.authority.fl_str_mv |
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dc.rights.driver.fl_str_mv |
Attribution-NonCommercial-NoDerivatives 4.0 International http://creativecommons.org/licenses/by-nc-nd/4.0/ info:eu-repo/semantics/openAccess |
rights_invalid_str_mv |
Attribution-NonCommercial-NoDerivatives 4.0 International http://creativecommons.org/licenses/by-nc-nd/4.0/ |
eu_rights_str_mv |
openAccess |
dc.publisher.none.fl_str_mv |
Universidade Federal de Santa Maria Centro de Ciências Naturais e Exatas |
dc.publisher.program.fl_str_mv |
Programa de Pós-Graduação em Ciências Biológicas: Bioquímica Toxicológica |
dc.publisher.initials.fl_str_mv |
UFSM |
dc.publisher.country.fl_str_mv |
Brasil |
dc.publisher.department.fl_str_mv |
Bioquímica |
publisher.none.fl_str_mv |
Universidade Federal de Santa Maria Centro de Ciências Naturais e Exatas |
dc.source.none.fl_str_mv |
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