Fenótipos envolvidos em comorbidades associadas às crises convulsivas: abordagens experimentais utilizando o peixe-zebra como organismo modelo
Autor(a) principal: | |
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Data de Publicação: | 2021 |
Tipo de documento: | Dissertação |
Idioma: | por |
Título da fonte: | Biblioteca Digital de Teses e Dissertações do UFSM |
Texto Completo: | http://repositorio.ufsm.br/handle/1/21822 |
Resumo: | Epilepsy is a neurological disease characterized by recurrent seizures that affects the cerebral homeostasis. This disease can generate negative consequences for the patient, such as behavioral and cognitive changes. Aggressiveness, anxiety, cognitive impairment, social isolation, and stress are examples of psychiatric comorbidities associated with epilepsy. Although this correlation has been well described in the literature, suggesting shared underlying mechanisms, it is necessary to characterize novel alternative model organisms to investigate the evolutionarily conserved bases associated with seizure-related comorbidities. The zebrafish (Danio rerio) is a model organism widely used in behavioral neuroscience, because this species shows conserved physiological features, well-characterized neurotransmitters, and a fully sequenced genome with a high degree of homology when compared to human genes. Here, we aimed to characterize the use of zebrafish models to study seizure-related comorbidities. In the first study, animals were exposed to pentylenetetrazole PTZ (10 mM) for 20 min to analyze the aggressive behavior in the mirror-induced aggression test at different time intervals (1h, 3h, 6h, 24h, 48h and 72h). In the second study, animals were exposed to PTZ in the same conditions and the effects on the exploratory pattern (novel tank diving test), anxiety-like behavior (light-dark test), memory consolidation (inhibitory avoidance test), shoaling behavior, and on whole-body cortisol levels were analyzed 24 h after the exposure. In the third study, to verify whether stress influences seizures behavioral responses, animals were acutely exposed to an intense stressor (conspecific alarm substance) for 5 min. The latency of animals to reach the clonic-like seizure behavior (score 4) induced by PTZ (7.5 mM), as well as the effects of conspecific alarm substance on the aversive behavior and whole-body cortisol levels were verified in stressed and non-stressed fish. Briefly, we verified that PTZ increased aggressive behavior, modified the exploratory pattern by disrupting the habituation to novelty, increased anxiety-like behavior, induced social isolation, and impaired memory consolidation. Furthermore, stress increased the susceptibility to seizures in zebrafish and we observed positive correlations between anxiety-like phenotypes and seizure-related behaviors. Overall, our results suggest that the zebrafish is an emerging model organism to investigate neuropsychiatric disorders that parallel those observed in epilepsy, serving as a potential tool to investigate the evolutionarily conserved mechanisms of seizures in vertebrates as well as to unravel future neuroprotective strategies. |
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2021-08-09T11:55:55Z2021-08-09T11:55:55Z2021-02-26http://repositorio.ufsm.br/handle/1/21822Epilepsy is a neurological disease characterized by recurrent seizures that affects the cerebral homeostasis. This disease can generate negative consequences for the patient, such as behavioral and cognitive changes. Aggressiveness, anxiety, cognitive impairment, social isolation, and stress are examples of psychiatric comorbidities associated with epilepsy. Although this correlation has been well described in the literature, suggesting shared underlying mechanisms, it is necessary to characterize novel alternative model organisms to investigate the evolutionarily conserved bases associated with seizure-related comorbidities. The zebrafish (Danio rerio) is a model organism widely used in behavioral neuroscience, because this species shows conserved physiological features, well-characterized neurotransmitters, and a fully sequenced genome with a high degree of homology when compared to human genes. Here, we aimed to characterize the use of zebrafish models to study seizure-related comorbidities. In the first study, animals were exposed to pentylenetetrazole PTZ (10 mM) for 20 min to analyze the aggressive behavior in the mirror-induced aggression test at different time intervals (1h, 3h, 6h, 24h, 48h and 72h). In the second study, animals were exposed to PTZ in the same conditions and the effects on the exploratory pattern (novel tank diving test), anxiety-like behavior (light-dark test), memory consolidation (inhibitory avoidance test), shoaling behavior, and on whole-body cortisol levels were analyzed 24 h after the exposure. In the third study, to verify whether stress influences seizures behavioral responses, animals were acutely exposed to an intense stressor (conspecific alarm substance) for 5 min. The latency of animals to reach the clonic-like seizure behavior (score 4) induced by PTZ (7.5 mM), as well as the effects of conspecific alarm substance on the aversive behavior and whole-body cortisol levels were verified in stressed and non-stressed fish. Briefly, we verified that PTZ increased aggressive behavior, modified the exploratory pattern by disrupting the habituation to novelty, increased anxiety-like behavior, induced social isolation, and impaired memory consolidation. Furthermore, stress increased the susceptibility to seizures in zebrafish and we observed positive correlations between anxiety-like phenotypes and seizure-related behaviors. Overall, our results suggest that the zebrafish is an emerging model organism to investigate neuropsychiatric disorders that parallel those observed in epilepsy, serving as a potential tool to investigate the evolutionarily conserved mechanisms of seizures in vertebrates as well as to unravel future neuroprotective strategies.A epilepsia é uma doença neurológica caracterizada por crises recorrentes que afetam a homeostase cerebral e geram consequências negativas para o paciente, como mudanças comportamentais e cognitivas. A agressividade, a ansiedade, o déficit cognitivo, o isolamento social e o estresse são exemplos de comorbidades psiquiátricas associadas com a epilepsia. Apesar de bem descrita essa correlação na literatura, sugerindo mecanismos subjacentes compartilhados, faz-se necessária a caracterização de novos organismos modelos para aprimorar os conhecimentos relacionados às bases evolutivamente conservadas das comorbidades associadas à epilepsia. O peixe-zebra (Danio rerio) é um organismo modelo amplamente utilizado na neurociência comportamental, pois apresenta aspectos fisiológicos conservados, neurotransmissores bem caracterizados, e genoma completamente sequenciado e similar aos genes humanos. O objetivo deste trabalho foi caracterizar o uso do peixe-zebra como organismo modelo para estudar comorbidades relacionadas à epilepsia em peixe-zebra. Primeiramente, os animais foram expostos ao agente convulsivante pentilenotetrazol (PTZ, 10 mM) por 20 min para analisar o comportamento agressivo no teste de agressividade induzida pelo espelho em diferentes intervalos de tempos após a exposição (1 h, 3 h, 6 h, 24 h, 48 h e 72 h). No segundo trabalho, os animais foram expostos ao PTZ nas mesmas condições, porém após 24 h foram analisados os efeitos da exposição única ao PTZ sobre o padrão exploratório no teste de exploração vertical eliciada por novidade, comportamento do tipo ansioso (teste claro-escuro), consolidação de memória (esquiva inibitória) e na interação social, bem como nos níveis de cortisol do corpo inteiro. No terceiro trabalho, a fim de verificar se o estresse tem influência nas respostas comportamentais do tipo convulsiva, os animais foram posteriormente expostos agudamente a um agente estressor intenso (substância de alarme de co-específicos, CAS) por 5 min. Posteriormente, foram verificadas a latência dos animais para atingir o comportamento convulsivo do tipo clônico (escore 4) induzido pela exposição ao PTZ (7,5 mM), bem como o papel da substância de alarme de co-específicos no comportamento aversivo e nos níveis de cortisol. Os resultados mostraram que a exposição ao PTZ aumentou o comportamento agressivo, modificou o padrão exploratório alterando a habituação a novidade, aumentou a ansiedade, causou embotamento social, bem como prejuízos na consolidação da memória, sem modificar os níveis de cortisol 24 h após a exposição. Além disso, nós também observamos que o estresse aumentou a susceptibilidade para crises convulsivas no peixe-zebra e verificamos uma correlação positiva entre o fenótipo do tipo ansioso com parâmetros relacionados à crise convulsiva. Em suma, nossos resultados sugerem que o peixe-zebra é um organismo modelo emergente para investigar alterações neuropsiquiátricas relacionadas às crises convulsivas, podendo servir como uma ferramenta para o estudo dos mecanismos evolutivamente conservados das crises convulsivas em vertebrados, bem como para futuras estratégias de neuroproteção.Conselho Nacional de Pesquisa e Desenvolvimento Científico e Tecnológico - CNPqCoordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPESFundação de Amparo à Pesquisa do Estado do Rio Grande do Sul - FAPERGSporUniversidade 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/openAccessCrises convulsivasPeixe-zebraComorbidadesEstresseCortisolSeizuresZebrafishComorbiditiesStressCNPQ::CIENCIAS BIOLOGICAS::BIOQUIMICAFenótipos envolvidos em comorbidades associadas às crises convulsivas: abordagens experimentais utilizando o peixe-zebra como organismo modeloPhenotypes involved in seizure-related comorbities: experimental approaches using the zebrafish as a model organisminfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesisRosemberg, Denis Broockhttp://lattes.cnpq.br/7713953979203056Barbosa, Nilda Berenice de VargasLuchiari , Ana Carolinahttp://lattes.cnpq.br/4148860749836110Marion, Julia Canzian200800000002600600600600600ccc7c308-e4c7-43a3-9992-827c7d8ffdfd6d72ce8a-c6e4-4806-9ecf-996f750906c951dd8038-260e-45c0-a23b-964111b21ed8859b1140-121e-4d2f-80aa-00c75dbbcc29reponame:Biblioteca Digital de Teses e Dissertações do UFSMinstname:Universidade Federal de Santa Maria (UFSM)instacron:UFSMORIGINALDIS_PPGCBBT_2021_MARION_JULIA.pdfDIS_PPGCBBT_2021_MARION_JULIA.pdfDissertaçãoapplication/pdf4938167http://repositorio.ufsm.br/bitstream/1/21822/1/DIS_PPGCBBT_2021_MARION_JULIA.pdf175d83583a7f715076d7839cb87c5dabMD51LICENSElicense.txtlicense.txttext/plain; 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dc.title.por.fl_str_mv |
Fenótipos envolvidos em comorbidades associadas às crises convulsivas: abordagens experimentais utilizando o peixe-zebra como organismo modelo |
dc.title.alternative.eng.fl_str_mv |
Phenotypes involved in seizure-related comorbities: experimental approaches using the zebrafish as a model organism |
title |
Fenótipos envolvidos em comorbidades associadas às crises convulsivas: abordagens experimentais utilizando o peixe-zebra como organismo modelo |
spellingShingle |
Fenótipos envolvidos em comorbidades associadas às crises convulsivas: abordagens experimentais utilizando o peixe-zebra como organismo modelo Marion, Julia Canzian Crises convulsivas Peixe-zebra Comorbidades Estresse Cortisol Seizures Zebrafish Comorbidities Stress CNPQ::CIENCIAS BIOLOGICAS::BIOQUIMICA |
title_short |
Fenótipos envolvidos em comorbidades associadas às crises convulsivas: abordagens experimentais utilizando o peixe-zebra como organismo modelo |
title_full |
Fenótipos envolvidos em comorbidades associadas às crises convulsivas: abordagens experimentais utilizando o peixe-zebra como organismo modelo |
title_fullStr |
Fenótipos envolvidos em comorbidades associadas às crises convulsivas: abordagens experimentais utilizando o peixe-zebra como organismo modelo |
title_full_unstemmed |
Fenótipos envolvidos em comorbidades associadas às crises convulsivas: abordagens experimentais utilizando o peixe-zebra como organismo modelo |
title_sort |
Fenótipos envolvidos em comorbidades associadas às crises convulsivas: abordagens experimentais utilizando o peixe-zebra como organismo modelo |
author |
Marion, Julia Canzian |
author_facet |
Marion, Julia Canzian |
author_role |
author |
dc.contributor.advisor1.fl_str_mv |
Rosemberg, Denis Broock |
dc.contributor.advisor1Lattes.fl_str_mv |
http://lattes.cnpq.br/7713953979203056 |
dc.contributor.referee1.fl_str_mv |
Barbosa, Nilda Berenice de Vargas |
dc.contributor.referee2.fl_str_mv |
Luchiari , Ana Carolina |
dc.contributor.authorLattes.fl_str_mv |
http://lattes.cnpq.br/4148860749836110 |
dc.contributor.author.fl_str_mv |
Marion, Julia Canzian |
contributor_str_mv |
Rosemberg, Denis Broock Barbosa, Nilda Berenice de Vargas Luchiari , Ana Carolina |
dc.subject.por.fl_str_mv |
Crises convulsivas Peixe-zebra Comorbidades Estresse Cortisol |
topic |
Crises convulsivas Peixe-zebra Comorbidades Estresse Cortisol Seizures Zebrafish Comorbidities Stress CNPQ::CIENCIAS BIOLOGICAS::BIOQUIMICA |
dc.subject.eng.fl_str_mv |
Seizures Zebrafish Comorbidities Stress |
dc.subject.cnpq.fl_str_mv |
CNPQ::CIENCIAS BIOLOGICAS::BIOQUIMICA |
description |
Epilepsy is a neurological disease characterized by recurrent seizures that affects the cerebral homeostasis. This disease can generate negative consequences for the patient, such as behavioral and cognitive changes. Aggressiveness, anxiety, cognitive impairment, social isolation, and stress are examples of psychiatric comorbidities associated with epilepsy. Although this correlation has been well described in the literature, suggesting shared underlying mechanisms, it is necessary to characterize novel alternative model organisms to investigate the evolutionarily conserved bases associated with seizure-related comorbidities. The zebrafish (Danio rerio) is a model organism widely used in behavioral neuroscience, because this species shows conserved physiological features, well-characterized neurotransmitters, and a fully sequenced genome with a high degree of homology when compared to human genes. Here, we aimed to characterize the use of zebrafish models to study seizure-related comorbidities. In the first study, animals were exposed to pentylenetetrazole PTZ (10 mM) for 20 min to analyze the aggressive behavior in the mirror-induced aggression test at different time intervals (1h, 3h, 6h, 24h, 48h and 72h). In the second study, animals were exposed to PTZ in the same conditions and the effects on the exploratory pattern (novel tank diving test), anxiety-like behavior (light-dark test), memory consolidation (inhibitory avoidance test), shoaling behavior, and on whole-body cortisol levels were analyzed 24 h after the exposure. In the third study, to verify whether stress influences seizures behavioral responses, animals were acutely exposed to an intense stressor (conspecific alarm substance) for 5 min. The latency of animals to reach the clonic-like seizure behavior (score 4) induced by PTZ (7.5 mM), as well as the effects of conspecific alarm substance on the aversive behavior and whole-body cortisol levels were verified in stressed and non-stressed fish. Briefly, we verified that PTZ increased aggressive behavior, modified the exploratory pattern by disrupting the habituation to novelty, increased anxiety-like behavior, induced social isolation, and impaired memory consolidation. Furthermore, stress increased the susceptibility to seizures in zebrafish and we observed positive correlations between anxiety-like phenotypes and seizure-related behaviors. Overall, our results suggest that the zebrafish is an emerging model organism to investigate neuropsychiatric disorders that parallel those observed in epilepsy, serving as a potential tool to investigate the evolutionarily conserved mechanisms of seizures in vertebrates as well as to unravel future neuroprotective strategies. |
publishDate |
2021 |
dc.date.accessioned.fl_str_mv |
2021-08-09T11:55:55Z |
dc.date.available.fl_str_mv |
2021-08-09T11:55:55Z |
dc.date.issued.fl_str_mv |
2021-02-26 |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/masterThesis |
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masterThesis |
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publishedVersion |
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http://repositorio.ufsm.br/handle/1/21822 |
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http://repositorio.ufsm.br/handle/1/21822 |
dc.language.iso.fl_str_mv |
por |
language |
por |
dc.relation.cnpq.fl_str_mv |
200800000002 |
dc.relation.confidence.fl_str_mv |
600 600 600 600 600 |
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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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UFSM |
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