Efeitos neurocomportamentais da taurina em modelos de exposição ao etanol e de crise convulsiva em peixe-zebra
Autor(a) principal: | |
---|---|
Data de Publicação: | 2018 |
Tipo de documento: | Dissertação |
Idioma: | por |
Título da fonte: | Manancial - Repositório Digital da UFSM |
Texto Completo: | http://repositorio.ufsm.br/handle/1/15102 |
Resumo: | Alternative translational models have been widely used in neuroscience for assessing several neurological and neuropsychiatric diseases. In this context, the emergent use of zebrafish (Danio rerio) has been relevant due to the high genetic conservation and the ability to perform high-throughput screens. Thus, in our first article, we aimed to evaluate the developing utility of zebrafish as an experimental model organism to later use evaluate the potential protector effects of taurine (TAU) in different situations. TAU is an endogenous molecule that has pleiotropic actions, such as neuromodulation, antioxidant activity, osmoregulation and membrane stabilization. The neuromodulatory action of TAU action occurs mainly through GABAA and glycine agonism. Several drugs can alter the functionality of GABAA receptors and modify the balance of inhibitory/excitatory synapses, such as ethanol (EtOH) and pentylenetetrazol (PTZ). Therefore, in our second and third works we analyzed the effects of TAU in preventing different EtOH-induced behavioral modifications, such as aggression, social interaction deficits,and changes in risk evaluation. Animals were exposed for 1 hour and divided into 8 groups: Control; TAU 42 mg/L; TAU 150 mg/L; TAU 400 mg/L; 0.25% EtOH (v/v); TAU 42/EtOH; TAU 150/EtOH and TAU 400/EtOH. Afterwards, fish were submitted to the aggression test, shoal behavior test, social preference test, and predator test. TAU exerted a biphasic effect on the aggressive behavior, where the lowest and highest concentration tested (42 and 400 mg/L) positively modulated aggression, while 150 mg/L exerted an anti-aggressive action. Additionally, temporal analysis of shoal behavior showed that EtOH alone and associated to TAU reduced social behaviors. However, in the social preference test only TAU 400/EtOH reduced conspecific preference. Regarding the aversive behavior, TAU alone and in association decreased the number of risk assessment in the predator area. Finally, we evaluated the protective role of TAU in PTZ-challenged animals and analyzed the occurence of seizures as well as changes in oxidative stress-related parameters. In this experiment, fish were pretreated with TAU (42, 150 or 400 mg / L) for 40 minutes and then exposed to PTZ for 20 minutes. Seizure scores were analyzed every 30 seconds during PTZ exposure and seizure intensity was quantified. Regarding theoxidative stress, the following parameters were analyzed: CAT, SOD, and GST activities, lipid and protein damage, as well as cellular viability and cellular death. TAU 150 mg/L attenuated PTZinduced seizures by reducing the seizure intensity and protecting against lipid and protein damage. Collectively, TAU modulates different neurochemical and behavioral responses depending on the concentration, suggesting a complex effect on different receptors and/or neural transduction pathways. |
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2018-12-13T21:16:54Z2018-12-13T21:16:54Z2018-05-22http://repositorio.ufsm.br/handle/1/15102Alternative translational models have been widely used in neuroscience for assessing several neurological and neuropsychiatric diseases. In this context, the emergent use of zebrafish (Danio rerio) has been relevant due to the high genetic conservation and the ability to perform high-throughput screens. Thus, in our first article, we aimed to evaluate the developing utility of zebrafish as an experimental model organism to later use evaluate the potential protector effects of taurine (TAU) in different situations. TAU is an endogenous molecule that has pleiotropic actions, such as neuromodulation, antioxidant activity, osmoregulation and membrane stabilization. The neuromodulatory action of TAU action occurs mainly through GABAA and glycine agonism. Several drugs can alter the functionality of GABAA receptors and modify the balance of inhibitory/excitatory synapses, such as ethanol (EtOH) and pentylenetetrazol (PTZ). Therefore, in our second and third works we analyzed the effects of TAU in preventing different EtOH-induced behavioral modifications, such as aggression, social interaction deficits,and changes in risk evaluation. Animals were exposed for 1 hour and divided into 8 groups: Control; TAU 42 mg/L; TAU 150 mg/L; TAU 400 mg/L; 0.25% EtOH (v/v); TAU 42/EtOH; TAU 150/EtOH and TAU 400/EtOH. Afterwards, fish were submitted to the aggression test, shoal behavior test, social preference test, and predator test. TAU exerted a biphasic effect on the aggressive behavior, where the lowest and highest concentration tested (42 and 400 mg/L) positively modulated aggression, while 150 mg/L exerted an anti-aggressive action. Additionally, temporal analysis of shoal behavior showed that EtOH alone and associated to TAU reduced social behaviors. However, in the social preference test only TAU 400/EtOH reduced conspecific preference. Regarding the aversive behavior, TAU alone and in association decreased the number of risk assessment in the predator area. Finally, we evaluated the protective role of TAU in PTZ-challenged animals and analyzed the occurence of seizures as well as changes in oxidative stress-related parameters. In this experiment, fish were pretreated with TAU (42, 150 or 400 mg / L) for 40 minutes and then exposed to PTZ for 20 minutes. Seizure scores were analyzed every 30 seconds during PTZ exposure and seizure intensity was quantified. Regarding theoxidative stress, the following parameters were analyzed: CAT, SOD, and GST activities, lipid and protein damage, as well as cellular viability and cellular death. TAU 150 mg/L attenuated PTZinduced seizures by reducing the seizure intensity and protecting against lipid and protein damage. Collectively, TAU modulates different neurochemical and behavioral responses depending on the concentration, suggesting a complex effect on different receptors and/or neural transduction pathways.O uso de modelos translacionais alternativos vem sendo amplamente utilizado na neurociência para o estudo de diversas doenças neurológicas e neuropsiquiátricas. Nesse contexto, o peixe-zebra (Danio rerio) ganha grande destaque uma vez que possui alta similaridade genética com seres humanos e permite a triagem de novos agentes farmacológicos de forma bastante eficiente. Assim, o objetivo do nosso primeiro trabalho foi avaliar as perspectivas do uso do peixe-zebra como organismo modelo a fim de posteriormente utilizá-lo para a avaliação do potencial protetor da taurina (TAU) em diferentes situações. A TAU é uma molécula que desempenha funções fisiológicas essenciais nos seres vivos, tais como neuromodulação, atividade antioxidante, osmoregulação e estabilização de membrana. Sua ação neuromoduladora ocorre principalmente através de sua ação agonista em receptor GABAA e de glicina. Diversas drogas são capazes de alterar a funcionalidade de receptores GABAA e modificar o balanço das sinapses inibitórias/excitatórias, tais como o etanol (EtOH) e o pentilenotetrazol (PTZ). Portanto, no segundo e no terceiro trabalho tivemos por objetivo analisar o papel da TAU sobre as alterações na agressividade, no comportamento social e na avaliação de risco induzidas pelo EtOH. Os animais foram expostos por 1 hora e divididos em 8 grupos: Controle; TAU 42 mg/L; TAU 150 mg/L; TAU 400 mg/L; EtOH 0,25% (v/v); TAU 42/EtOH; TAU 150/EtOH e TAU 400/EtOH. Posteriormente, os animais foram submetidos ao teste de agressividade, comportamento em cardume, preferência social e ao teste do predador. De modo geral, a TAU apresentou um efeito bifásico no comportamento agressivo, onde a menor e a maior concentração testada (42 e 400 mg/L) modularam positivamente a agressão, enquanto que 150 mg/L exerceu uma ação anti-agressiva. Além disso, análise temporal do comportamento em cardume mostrou que EtOH sozinho e associado à TAU apresentam uma redução do comportamento social. No entanto, no teste de preferência social somente TAU 400/EtOH reduziram a preferência por coespecíficos. Em relação ao comportamento aversivo do peixe-zebra, TAU per se e em associação diminuiu as avaliações de risco na área do predador. Por fim, avaliamos o papel protetor da TAU frente às crises convulsivas induzidas pelo PTZ através da análise dos estágios de crise convulsiva, bem como dos parâmetros relacionados ao estresse oxidativo. Os peixes foram pré-tratados com TAU (42, 150 ou 400 mg/L) por 40 minutos e então expostos ao PTZ por 20 minutos, onde os escores de crise convulsiva foram analisados a cada 30 segundos durante a exposição e a intensidade da crise convulsiva mensurada. Para a análise de estresse oxidativo, os seguintes parâmetros foram quantificados: atividade das enzimas CAT, SOD e GST cerebral,níveis de peroxidação lipídica, carbonilação de proteínas, viabilidade e morte celular. Os resultados mostraram que a TAU 150 mg/L atenuou as crises convulsivas induzidas pelo PTZ, diminuindo a intensidade das crises convulsivas e prevenindo o dano oxidativo. Assim, a TAU é capaz de modular diferentes respostas neuroquímicas e comportamentais dependendo da concentração, sugerindo um complexo efeito da TAU em diferentes receptores e/ou em vias de transdução de sinal no SNC.Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPESporUniversidade 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/openAccessAgressividadeComportamento aversivoComportamento socialEpilepsiasAversive behaviorsAggressivenessSocial behaviorEpilepsyCNPQ::CIENCIAS BIOLOGICAS::BIOQUIMICAEfeitos neurocomportamentais da taurina em modelos de exposição ao etanol e de crise convulsiva em peixe-zebraNeurobehavioral effects of taurine in ethanol exposure models and seizures in zebrafishinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesisRosemberg, Denis Broockhttp://lattes.cnpq.br/7713953979203056Oliveira, Diogo Losch dehttp://lattes.cnpq.br/3056695127432911Fachinetto, Roseleihttp://lattes.cnpq.br/7203076675431306http://lattes.cnpq.br/0276537504451928Fontana, Barbara Dotto200800000002600ccc7c308-e4c7-43a3-9992-827c7d8ffdfd8d5e6ea4-679e-40e5-be3e-8edf32f7794e586ac01b-276a-4195-8424-4672be46ceb46a615e4f-285a-4d77-aeb6-a33cd9c07f80reponame:Manancial - Repositório Digital da UFSMinstname:Universidade Federal de Santa Maria (UFSM)instacron:UFSMORIGINALDIS_PPGCB_2018_FONTANA_BARBARA.pdfDIS_PPGCB_2018_FONTANA_BARBARA.pdfDissertação de Mestradoapplication/pdf8504521http://repositorio.ufsm.br/bitstream/1/15102/1/DIS_PPGCB_2018_FONTANA_BARBARA.pdfd6d049dd449b69d1ec56bc292af98642MD51CC-LICENSElicense_rdflicense_rdfapplication/rdf+xml; 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dc.title.por.fl_str_mv |
Efeitos neurocomportamentais da taurina em modelos de exposição ao etanol e de crise convulsiva em peixe-zebra |
dc.title.alternative.eng.fl_str_mv |
Neurobehavioral effects of taurine in ethanol exposure models and seizures in zebrafish |
title |
Efeitos neurocomportamentais da taurina em modelos de exposição ao etanol e de crise convulsiva em peixe-zebra |
spellingShingle |
Efeitos neurocomportamentais da taurina em modelos de exposição ao etanol e de crise convulsiva em peixe-zebra Fontana, Barbara Dotto Agressividade Comportamento aversivo Comportamento social Epilepsias Aversive behaviors Aggressiveness Social behavior Epilepsy CNPQ::CIENCIAS BIOLOGICAS::BIOQUIMICA |
title_short |
Efeitos neurocomportamentais da taurina em modelos de exposição ao etanol e de crise convulsiva em peixe-zebra |
title_full |
Efeitos neurocomportamentais da taurina em modelos de exposição ao etanol e de crise convulsiva em peixe-zebra |
title_fullStr |
Efeitos neurocomportamentais da taurina em modelos de exposição ao etanol e de crise convulsiva em peixe-zebra |
title_full_unstemmed |
Efeitos neurocomportamentais da taurina em modelos de exposição ao etanol e de crise convulsiva em peixe-zebra |
title_sort |
Efeitos neurocomportamentais da taurina em modelos de exposição ao etanol e de crise convulsiva em peixe-zebra |
author |
Fontana, Barbara Dotto |
author_facet |
Fontana, Barbara Dotto |
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 |
Oliveira, Diogo Losch de |
dc.contributor.referee1Lattes.fl_str_mv |
http://lattes.cnpq.br/3056695127432911 |
dc.contributor.referee2.fl_str_mv |
Fachinetto, Roselei |
dc.contributor.referee2Lattes.fl_str_mv |
http://lattes.cnpq.br/7203076675431306 |
dc.contributor.authorLattes.fl_str_mv |
http://lattes.cnpq.br/0276537504451928 |
dc.contributor.author.fl_str_mv |
Fontana, Barbara Dotto |
contributor_str_mv |
Rosemberg, Denis Broock Oliveira, Diogo Losch de Fachinetto, Roselei |
dc.subject.por.fl_str_mv |
Agressividade Comportamento aversivo Comportamento social Epilepsias |
topic |
Agressividade Comportamento aversivo Comportamento social Epilepsias Aversive behaviors Aggressiveness Social behavior Epilepsy CNPQ::CIENCIAS BIOLOGICAS::BIOQUIMICA |
dc.subject.eng.fl_str_mv |
Aversive behaviors Aggressiveness Social behavior |
dc.subject.fra.fl_str_mv |
Epilepsy |
dc.subject.cnpq.fl_str_mv |
CNPQ::CIENCIAS BIOLOGICAS::BIOQUIMICA |
description |
Alternative translational models have been widely used in neuroscience for assessing several neurological and neuropsychiatric diseases. In this context, the emergent use of zebrafish (Danio rerio) has been relevant due to the high genetic conservation and the ability to perform high-throughput screens. Thus, in our first article, we aimed to evaluate the developing utility of zebrafish as an experimental model organism to later use evaluate the potential protector effects of taurine (TAU) in different situations. TAU is an endogenous molecule that has pleiotropic actions, such as neuromodulation, antioxidant activity, osmoregulation and membrane stabilization. The neuromodulatory action of TAU action occurs mainly through GABAA and glycine agonism. Several drugs can alter the functionality of GABAA receptors and modify the balance of inhibitory/excitatory synapses, such as ethanol (EtOH) and pentylenetetrazol (PTZ). Therefore, in our second and third works we analyzed the effects of TAU in preventing different EtOH-induced behavioral modifications, such as aggression, social interaction deficits,and changes in risk evaluation. Animals were exposed for 1 hour and divided into 8 groups: Control; TAU 42 mg/L; TAU 150 mg/L; TAU 400 mg/L; 0.25% EtOH (v/v); TAU 42/EtOH; TAU 150/EtOH and TAU 400/EtOH. Afterwards, fish were submitted to the aggression test, shoal behavior test, social preference test, and predator test. TAU exerted a biphasic effect on the aggressive behavior, where the lowest and highest concentration tested (42 and 400 mg/L) positively modulated aggression, while 150 mg/L exerted an anti-aggressive action. Additionally, temporal analysis of shoal behavior showed that EtOH alone and associated to TAU reduced social behaviors. However, in the social preference test only TAU 400/EtOH reduced conspecific preference. Regarding the aversive behavior, TAU alone and in association decreased the number of risk assessment in the predator area. Finally, we evaluated the protective role of TAU in PTZ-challenged animals and analyzed the occurence of seizures as well as changes in oxidative stress-related parameters. In this experiment, fish were pretreated with TAU (42, 150 or 400 mg / L) for 40 minutes and then exposed to PTZ for 20 minutes. Seizure scores were analyzed every 30 seconds during PTZ exposure and seizure intensity was quantified. Regarding theoxidative stress, the following parameters were analyzed: CAT, SOD, and GST activities, lipid and protein damage, as well as cellular viability and cellular death. TAU 150 mg/L attenuated PTZinduced seizures by reducing the seizure intensity and protecting against lipid and protein damage. Collectively, TAU modulates different neurochemical and behavioral responses depending on the concentration, suggesting a complex effect on different receptors and/or neural transduction pathways. |
publishDate |
2018 |
dc.date.accessioned.fl_str_mv |
2018-12-13T21:16:54Z |
dc.date.available.fl_str_mv |
2018-12-13T21:16:54Z |
dc.date.issued.fl_str_mv |
2018-05-22 |
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://repositorio.ufsm.br/handle/1/15102 |
url |
http://repositorio.ufsm.br/handle/1/15102 |
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 |
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 |
bitstream.url.fl_str_mv |
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