Alterações comportamentais mediadas pelo etanol em peixe-zebra: influência do estresse oxidativo, disfunção mitocondrial e modulação serotoninérgica

Detalhes bibliográficos
Autor(a) principal: Müller, Talise Ellwanger
Data de Publicação: 2020
Tipo de documento: Tese
Idioma: por
Título da fonte: Manancial - Repositório Digital da UFSM
Texto Completo: http://repositorio.ufsm.br/handle/1/22012
Resumo: Ethanol consumption is a serious public health problem due to the negative impacts that affect individuals and society. Because the mechanism of action of ethanol in the central nervous system is complex and not fully understood, the drugs available to treat alcohol use-related disorders are not effective. Thus, the validation of new experimental models for translational studies of alcohol-induced disorders is important. The zebrafish (Danio rerio) has been used successfully to investigate the mechanisms related to ethanol abuse and addiction. However, several biochemical and behavioral features of ethanol exposure protocols in zebrafish still need to be explored. In the present study, we used acute and chronic ethanol exposure protocols in zebrafish to investigate biochemical aspects related to oxidative stress, bioenergetics, and the potential involvement of the serotonergic system in the neurobehavioral responses induced by alcohol. In a first study, we found that chronic exposure to ethanol (1.0% v/v) for 20 minutes for 8 days induced an anxiogenic effect, increasing social behavior and promoting oxidative stress. When assessing the effects of ethanol on mitochondrial respiration in the second study, we observed that acute exposure to ethanol (1.0% v/v for 1 hour) stimulated the oxidative phosphorylation process and increased the functionality of mitochondria in zebrafish brain, while the chronic exposure, similar to the protocol of the first study, impaired the transfer of electrons between I and II complexes of the mitochondrial respiratory chain. In the third study, we evaluated the involvement of the serotonergic system in acute responses to ethanol. Ethanol-induced aggressive behavior (0.25% v/v for 1 hour) is modulated by the serotonergic pathway with the main action of the 5-HT2A receptor, while the anxiolytic-like responses observed after exposure to a moderate concentration of ethanol (0.5% v/v for 1 hour) are modulated mainly by the 5-HT1B receptor. Depressive responses induced by ethanol (1.0% v/v for 1 hour) were not modulated by serotonergic drugs. In summary, similarly to what occurs in humans, we found that the responses mediated by ethanol in different experimental protocols involve changes in social behavior, oxidative stress, mitochondrial dysfunction, and serotonergic modulation in zebrafish. Our findings help elucidate the central mechanisms of action of ethanol and associated behaviors, reinforcing the predictive, face, and construct value of ethanol exposure models in zebrafish. These new results will allow the expansion of translational studies using this model organism in scientific research aimed at elucidating the mechanisms underlying the alcohol abuse and addiction.
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spelling Alterações comportamentais mediadas pelo etanol em peixe-zebra: influência do estresse oxidativo, disfunção mitocondrial e modulação serotoninérgicaEthanol-induced behavioral changes in zebrafish: influence of oxidative stress, mitochondrial dysfunction, and serotonergic modulationÁlcoolPeixe-zebraComportamentoBioquímicaSerotoninaAlcoholZebrafishBehaviorBiochemistrySerotoninCNPQ::CIENCIAS BIOLOGICAS::BIOQUIMICAEthanol consumption is a serious public health problem due to the negative impacts that affect individuals and society. Because the mechanism of action of ethanol in the central nervous system is complex and not fully understood, the drugs available to treat alcohol use-related disorders are not effective. Thus, the validation of new experimental models for translational studies of alcohol-induced disorders is important. The zebrafish (Danio rerio) has been used successfully to investigate the mechanisms related to ethanol abuse and addiction. However, several biochemical and behavioral features of ethanol exposure protocols in zebrafish still need to be explored. In the present study, we used acute and chronic ethanol exposure protocols in zebrafish to investigate biochemical aspects related to oxidative stress, bioenergetics, and the potential involvement of the serotonergic system in the neurobehavioral responses induced by alcohol. In a first study, we found that chronic exposure to ethanol (1.0% v/v) for 20 minutes for 8 days induced an anxiogenic effect, increasing social behavior and promoting oxidative stress. When assessing the effects of ethanol on mitochondrial respiration in the second study, we observed that acute exposure to ethanol (1.0% v/v for 1 hour) stimulated the oxidative phosphorylation process and increased the functionality of mitochondria in zebrafish brain, while the chronic exposure, similar to the protocol of the first study, impaired the transfer of electrons between I and II complexes of the mitochondrial respiratory chain. In the third study, we evaluated the involvement of the serotonergic system in acute responses to ethanol. Ethanol-induced aggressive behavior (0.25% v/v for 1 hour) is modulated by the serotonergic pathway with the main action of the 5-HT2A receptor, while the anxiolytic-like responses observed after exposure to a moderate concentration of ethanol (0.5% v/v for 1 hour) are modulated mainly by the 5-HT1B receptor. Depressive responses induced by ethanol (1.0% v/v for 1 hour) were not modulated by serotonergic drugs. In summary, similarly to what occurs in humans, we found that the responses mediated by ethanol in different experimental protocols involve changes in social behavior, oxidative stress, mitochondrial dysfunction, and serotonergic modulation in zebrafish. Our findings help elucidate the central mechanisms of action of ethanol and associated behaviors, reinforcing the predictive, face, and construct value of ethanol exposure models in zebrafish. These new results will allow the expansion of translational studies using this model organism in scientific research aimed at elucidating the mechanisms underlying the alcohol abuse and addiction.Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPESO consumo de etanol é um grave problema de saúde pública devido aos impactos negativos que causa nos indivíduos e na sociedade. Pelo fato do mecanismo de ação do etanol no sistema nervoso central ser complexo e não totalmente compreendido, os medicamentos disponíveis para tratar as desordens relacionadas ao uso de álcool não apresentam boa eficácia. Assim, a validação de novos modelos experimentais para o estudo translacional das desordens induzidas pelo álcool é importante. O peixe-zebra (Danio rerio) tem sido utilizado com sucesso para investigar os mecanismos relacionados ao abuso e vício ao etanol. Porém, muitos aspectos bioquímicos e comportamentais ainda necessitam ser explorados e avaliados dentro dos modelos de exposição ao etanol em peixe-zebra. No presente estudo, utilizamos protocolos agudos e crônicos de exposição ao etanol em peixe-zebra com o objetivo de investigar aspectos relacionados ao estresse oxidativo, bioenergética e o potencial envolvimento do sistema serotoninérgico nas respostas neurocomportamentais induzidas pelo álcool. Em um primeiro estudo, verificamos que a exposição crônica ao etanol (1.0% v/v) por 20 minutos durante 8 dias gerou um efeito do tipo ansiogênico, aumentando o comportamento social e promovendo estresse oxidativo. Ao avaliar efeitos do etanol sobre a respiração mitocondrial no segundo estudo, observamos que a exposição aguda ao etanol (1.0% v/v por 1 hora) estimulou o processo de fosforilação oxidativa e aumentou a funcionalidade da mitocôndria em encéfalo de peixe-zebra, enquanto que a exposição crônica, similar ao protocolo do primeiro estudo, prejudicou a transferência de elétrons entre os complexos I e II da cadeia respiratória mitocondrial. No terceiro estudo, no qual avaliamos o envolvimento do sistema serotoninérgico nas respostas agudas ao etanol, verificamos que o comportamento de agressividade induzido pelo etanol (0.25% v/v por 1 hora) é modulado pela via serotoninérgica com ação principal do receptor 5-HT2A, enquanto que as respostas do tipo ansiolíticas observadas após a exposição a uma concentração moderada de etanol (0.5% v/v por 1 hora) são moduladas principalmente pelo receptor 5-HT1B. As respostas depressoras induzidas pelo etanol (1.0% v/v por 1 hora) não foram moduladas por fármacos com ação serotoninérgica. Em suma, de modo similar ao que ocorre em humanos, verificamos que as repostas mediadas pelo etanol em diferentes protocolos experimentais envolvem alterações no comportamento social, estresse oxidativo, disfunção mitocondrial e modulação serotoninérgica em peixe-zebra. Nossos achados auxiliam na elucidação dos mecanismos centrais de ação do etanol e comportamentos associados, reforçando o valor preditivo, de face e de construto dos modelos de exposição ao etanol em peixe-zebra. Esses novos resultados permitirão a expansão dos estudos translacionais utilizando este organismo modelo em pesquisas científicas visando elucidar os mecanismos subjacentes ao abuso e vício ao etanol.Universidade Federal de Santa MariaBrasilBioquímicaUFSMPrograma de Pós-Graduação em Ciências Biológicas: Bioquímica ToxicológicaCentro de Ciências Naturais e ExatasRosemberg, Denis Broockhttp://lattes.cnpq.br/7713953979203056Fachinetto , RoseleiOliveira, Sara Marchesan deRico, Eduardo PachecoBogo, Mauricio ReisMüller, Talise Ellwanger2021-08-20T11:51:42Z2021-08-20T11:51:42Z2020-07-24info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/doctoralThesisapplication/pdfhttp://repositorio.ufsm.br/handle/1/22012porAttribution-NonCommercial-NoDerivatives 4.0 Internationalhttp://creativecommons.org/licenses/by-nc-nd/4.0/info:eu-repo/semantics/openAccessreponame:Manancial - Repositório Digital da UFSMinstname:Universidade Federal de Santa Maria (UFSM)instacron:UFSM2021-08-21T06:03:08Zoai:repositorio.ufsm.br:1/22012Biblioteca Digital de Teses e Dissertaçõeshttps://repositorio.ufsm.br/ONGhttps://repositorio.ufsm.br/oai/requestatendimento.sib@ufsm.br||tedebc@gmail.comopendoar:2021-08-21T06:03:08Manancial - Repositório Digital da UFSM - Universidade Federal de Santa Maria (UFSM)false
dc.title.none.fl_str_mv Alterações comportamentais mediadas pelo etanol em peixe-zebra: influência do estresse oxidativo, disfunção mitocondrial e modulação serotoninérgica
Ethanol-induced behavioral changes in zebrafish: influence of oxidative stress, mitochondrial dysfunction, and serotonergic modulation
title Alterações comportamentais mediadas pelo etanol em peixe-zebra: influência do estresse oxidativo, disfunção mitocondrial e modulação serotoninérgica
spellingShingle Alterações comportamentais mediadas pelo etanol em peixe-zebra: influência do estresse oxidativo, disfunção mitocondrial e modulação serotoninérgica
Müller, Talise Ellwanger
Álcool
Peixe-zebra
Comportamento
Bioquímica
Serotonina
Alcohol
Zebrafish
Behavior
Biochemistry
Serotonin
CNPQ::CIENCIAS BIOLOGICAS::BIOQUIMICA
title_short Alterações comportamentais mediadas pelo etanol em peixe-zebra: influência do estresse oxidativo, disfunção mitocondrial e modulação serotoninérgica
title_full Alterações comportamentais mediadas pelo etanol em peixe-zebra: influência do estresse oxidativo, disfunção mitocondrial e modulação serotoninérgica
title_fullStr Alterações comportamentais mediadas pelo etanol em peixe-zebra: influência do estresse oxidativo, disfunção mitocondrial e modulação serotoninérgica
title_full_unstemmed Alterações comportamentais mediadas pelo etanol em peixe-zebra: influência do estresse oxidativo, disfunção mitocondrial e modulação serotoninérgica
title_sort Alterações comportamentais mediadas pelo etanol em peixe-zebra: influência do estresse oxidativo, disfunção mitocondrial e modulação serotoninérgica
author Müller, Talise Ellwanger
author_facet Müller, Talise Ellwanger
author_role author
dc.contributor.none.fl_str_mv Rosemberg, Denis Broock
http://lattes.cnpq.br/7713953979203056
Fachinetto , Roselei
Oliveira, Sara Marchesan de
Rico, Eduardo Pacheco
Bogo, Mauricio Reis
dc.contributor.author.fl_str_mv Müller, Talise Ellwanger
dc.subject.por.fl_str_mv Álcool
Peixe-zebra
Comportamento
Bioquímica
Serotonina
Alcohol
Zebrafish
Behavior
Biochemistry
Serotonin
CNPQ::CIENCIAS BIOLOGICAS::BIOQUIMICA
topic Álcool
Peixe-zebra
Comportamento
Bioquímica
Serotonina
Alcohol
Zebrafish
Behavior
Biochemistry
Serotonin
CNPQ::CIENCIAS BIOLOGICAS::BIOQUIMICA
description Ethanol consumption is a serious public health problem due to the negative impacts that affect individuals and society. Because the mechanism of action of ethanol in the central nervous system is complex and not fully understood, the drugs available to treat alcohol use-related disorders are not effective. Thus, the validation of new experimental models for translational studies of alcohol-induced disorders is important. The zebrafish (Danio rerio) has been used successfully to investigate the mechanisms related to ethanol abuse and addiction. However, several biochemical and behavioral features of ethanol exposure protocols in zebrafish still need to be explored. In the present study, we used acute and chronic ethanol exposure protocols in zebrafish to investigate biochemical aspects related to oxidative stress, bioenergetics, and the potential involvement of the serotonergic system in the neurobehavioral responses induced by alcohol. In a first study, we found that chronic exposure to ethanol (1.0% v/v) for 20 minutes for 8 days induced an anxiogenic effect, increasing social behavior and promoting oxidative stress. When assessing the effects of ethanol on mitochondrial respiration in the second study, we observed that acute exposure to ethanol (1.0% v/v for 1 hour) stimulated the oxidative phosphorylation process and increased the functionality of mitochondria in zebrafish brain, while the chronic exposure, similar to the protocol of the first study, impaired the transfer of electrons between I and II complexes of the mitochondrial respiratory chain. In the third study, we evaluated the involvement of the serotonergic system in acute responses to ethanol. Ethanol-induced aggressive behavior (0.25% v/v for 1 hour) is modulated by the serotonergic pathway with the main action of the 5-HT2A receptor, while the anxiolytic-like responses observed after exposure to a moderate concentration of ethanol (0.5% v/v for 1 hour) are modulated mainly by the 5-HT1B receptor. Depressive responses induced by ethanol (1.0% v/v for 1 hour) were not modulated by serotonergic drugs. In summary, similarly to what occurs in humans, we found that the responses mediated by ethanol in different experimental protocols involve changes in social behavior, oxidative stress, mitochondrial dysfunction, and serotonergic modulation in zebrafish. Our findings help elucidate the central mechanisms of action of ethanol and associated behaviors, reinforcing the predictive, face, and construct value of ethanol exposure models in zebrafish. These new results will allow the expansion of translational studies using this model organism in scientific research aimed at elucidating the mechanisms underlying the alcohol abuse and addiction.
publishDate 2020
dc.date.none.fl_str_mv 2020-07-24
2021-08-20T11:51:42Z
2021-08-20T11:51:42Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/doctoralThesis
format doctoralThesis
status_str publishedVersion
dc.identifier.uri.fl_str_mv http://repositorio.ufsm.br/handle/1/22012
url http://repositorio.ufsm.br/handle/1/22012
dc.language.iso.fl_str_mv por
language por
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.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Universidade Federal de Santa Maria
Brasil
Bioquímica
UFSM
Programa de Pós-Graduação em Ciências Biológicas: Bioquímica Toxicológica
Centro de Ciências Naturais e Exatas
publisher.none.fl_str_mv Universidade Federal de Santa Maria
Brasil
Bioquímica
UFSM
Programa de Pós-Graduação em Ciências Biológicas: Bioquímica Toxicológica
Centro de Ciências Naturais e Exatas
dc.source.none.fl_str_mv reponame:Manancial - Repositório Digital da UFSM
instname:Universidade Federal de Santa Maria (UFSM)
instacron:UFSM
instname_str Universidade Federal de Santa Maria (UFSM)
instacron_str UFSM
institution UFSM
reponame_str Manancial - Repositório Digital da UFSM
collection Manancial - Repositório Digital da UFSM
repository.name.fl_str_mv Manancial - Repositório Digital da UFSM - Universidade Federal de Santa Maria (UFSM)
repository.mail.fl_str_mv atendimento.sib@ufsm.br||tedebc@gmail.com
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