Alterações comportamentais e metabólicas induzidas pelo estilo de vida: ação do disseleneto de m-trifluormetil-difenila em camundongos
Ano de defesa: | 2023 |
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Autor(a) principal: | |
Orientador(a): | |
Banca de defesa: | , , , |
Tipo de documento: | Tese |
Tipo de acesso: | Acesso aberto |
Idioma: | por |
Instituição de defesa: |
Universidade Federal de Santa Maria
Centro de Ciências Naturais e Exatas |
Programa de Pós-Graduação: |
Programa de Pós-Graduação em Ciências Biológicas: Bioquímica Toxicológica
|
Departamento: |
Bioquímica
|
País: |
Brasil
|
Palavras-chave em Português: | |
Palavras-chave em Inglês: | |
Área do conhecimento CNPq: | |
Link de acesso: | http://repositorio.ufsm.br/handle/1/28890 |
Resumo: | Modern lifestyle is composed of unhealthy habits, including energy-dense food and ethanol intake. The increase in these habits has been related to depression, anxiety, and obesity. Besides, pharmacological approaches are needed to treat lifestyle-related diseases. m-Trifluoromethyldiphenyl diselenide [(m-CF3-PhSe)2] is a low-toxicity compound with pharmacological properties, including anti-inflammatory, antidepressive- and anxiolytic-like in animal models. This thesis aimed to evaluate (m-CF3-PhSe)2 effects on depressive and anxiolytic-like phenotypes and markers of metabolism of carbohydrates and lipids in young mice exposed to a lifestyle model: association of an energy-dense diet and ethanol sporadic intake. Firstly, for article 1, article 2 and article 3 25 days old Swiss male mice (CEUA: 7141061018 e 4849060420) were exposed to an energy-dense diet until postnatal day 66. From the postnatal day 45 to 60, the animals received, by the intragastric (i.g) route, an ethanol sporadic regimen, 3 times a week at 2g/kg. Posteriorly, (m-CF3-PhSe)2 was administered via i.g. for 7 days. From postnatal days 67 to 68, some animals were subjected to behavioral tests predictive of depressive-like behavior (article 1), whereas others performed anxiety-like tests (article 2). On day 69, the animals were euthanized and the cerebral cortex (article 1 and article 2), the liver, the blood, and the hypothalamus (article 3) were collected for analyses. The results of article 1 demonstrated that the modulation of the opioid system and the antioxidant effect in the cerebral cortex of mice contributed to the (m-CF3-PhSe)2 effectiveness in the lifestyle depression-induced model. In article 2, the results revealed that (m-CF3-PhSe)2 elicited an anxiolytic-like effect associated with the modulation of NMDAR-mediated neurotoxicity, neuroinflammation and by the improvement of synaptic plasticity in the cerebral cortex of mice exposed to the lifestyle model. Finally, (m-CF3-PhSe)2 reversed the accumulation of relative abdominal white adipose tissue to body weight, which was accompanied by hepatic lipotoxicity (article 3). Furthermore, (m-CF3-PhSe)2 modulated glycolytic pathway markers, hepatic insulin signaling, and counteracted hypothalamic inflammation in young mice subjected to the lifestyle-induced model. Besides, in article 3, (m-CF3-PhSe)2 modulated hypothalamic insulin, ghrelin, and leptin receptor levels of mice exposed to the lifestyle model. The results of this thesis contributed to a better comprehension of (m-CF3-PhSe)2 action against depressive- and anxiety-like phenotypes and against the lipotoxicity, insulin signaling, and glycolytic pathway markers in the liver and the hypothalamic inflammation induced by the lifestyle model in young mice. |
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2023-05-02T14:53:37Z2023-05-02T14:53:37Z2023-03-24http://repositorio.ufsm.br/handle/1/28890Modern lifestyle is composed of unhealthy habits, including energy-dense food and ethanol intake. The increase in these habits has been related to depression, anxiety, and obesity. Besides, pharmacological approaches are needed to treat lifestyle-related diseases. m-Trifluoromethyldiphenyl diselenide [(m-CF3-PhSe)2] is a low-toxicity compound with pharmacological properties, including anti-inflammatory, antidepressive- and anxiolytic-like in animal models. This thesis aimed to evaluate (m-CF3-PhSe)2 effects on depressive and anxiolytic-like phenotypes and markers of metabolism of carbohydrates and lipids in young mice exposed to a lifestyle model: association of an energy-dense diet and ethanol sporadic intake. Firstly, for article 1, article 2 and article 3 25 days old Swiss male mice (CEUA: 7141061018 e 4849060420) were exposed to an energy-dense diet until postnatal day 66. From the postnatal day 45 to 60, the animals received, by the intragastric (i.g) route, an ethanol sporadic regimen, 3 times a week at 2g/kg. Posteriorly, (m-CF3-PhSe)2 was administered via i.g. for 7 days. From postnatal days 67 to 68, some animals were subjected to behavioral tests predictive of depressive-like behavior (article 1), whereas others performed anxiety-like tests (article 2). On day 69, the animals were euthanized and the cerebral cortex (article 1 and article 2), the liver, the blood, and the hypothalamus (article 3) were collected for analyses. The results of article 1 demonstrated that the modulation of the opioid system and the antioxidant effect in the cerebral cortex of mice contributed to the (m-CF3-PhSe)2 effectiveness in the lifestyle depression-induced model. In article 2, the results revealed that (m-CF3-PhSe)2 elicited an anxiolytic-like effect associated with the modulation of NMDAR-mediated neurotoxicity, neuroinflammation and by the improvement of synaptic plasticity in the cerebral cortex of mice exposed to the lifestyle model. Finally, (m-CF3-PhSe)2 reversed the accumulation of relative abdominal white adipose tissue to body weight, which was accompanied by hepatic lipotoxicity (article 3). Furthermore, (m-CF3-PhSe)2 modulated glycolytic pathway markers, hepatic insulin signaling, and counteracted hypothalamic inflammation in young mice subjected to the lifestyle-induced model. Besides, in article 3, (m-CF3-PhSe)2 modulated hypothalamic insulin, ghrelin, and leptin receptor levels of mice exposed to the lifestyle model. The results of this thesis contributed to a better comprehension of (m-CF3-PhSe)2 action against depressive- and anxiety-like phenotypes and against the lipotoxicity, insulin signaling, and glycolytic pathway markers in the liver and the hypothalamic inflammation induced by the lifestyle model in young mice.O estilo de vida moderno é composto por hábitos não saudáveis, incluindo o consumo de alimentos de alta densidade energética e de etanol. O crescente aumento destes hábitos tem sido relacionado ao desenvolvimento de doenças como a depressão, a ansiedade e a obesidade. Ademais, abordagens farmacológicas são requeridas ao tratamento de doenças relacionadas ao estilo de vida. O disseleneto de m-trifluormetildifenila [(m-CF3-PhSe)2], apresenta baixa toxicidade e propriedades farmacológicas como efeito do tipo antidepressivo, ansiolítico e antiinflamatório em modelos animais. Com isso, o objetivo desta tese foi avaliar os efeitos do (mCF3-PhSe)2 sobre o fenótipo do tipo depressivo e ansioso, bem como sobre marcadores do metabolismo de carboidratos e lipídeos de camundongos jovens expostos a um modelo de estilo de vida: associação de uma dieta de alta densidade energética e consumo esporádico de etanol. Inicialmente, tanto para o artigo 1, artigo 2 e artigo 3 camundongos Swiss machos de 25 dias (CEUA: 7141061018 e 4849060420) foram expostos a uma dieta de alta densidade energética até o dia 66 de idade. A partir do dia 45 de idade, os animais receberam etanol 2g/kg em regime esporádico de 3 vezes por semana pela via intragástrica (i.g) até o dia 60 de idade. Posteriormente, o (m-CF3-PhSe)2 foi administrado via i.g. por 7 dias. Durante os dias 67 e 68, alguns animais passaram pelos testes comportamentais preditivos de comportamento do tipo depressivo (artigo 1), enquanto outros foram submetidos aos testes relacionados ao fenótipo do tipo ansioso (artigo 2). No dia 69, ocorreu a eutanásia dos animais e o córtex cerebral (artigo 1 e artigo 2) o fígado, o sangue e o hipotálamo (artigo 3) foram coletados para análises. Os resultados do artigo 1 demonstraram que a modulação do sistema opióide e o efeito antioxidante do (m-CF3-PhSe)2 em córtex cerebral contribuem para a eficácia do composto no modelo de depressão induzido pelo estilo de vida em camundongos. No artigo 2, os resultados revelaram que o (m-CF3-PhSe)2 apresentou efeito do tipo ansiolítico associado a modulação da neurotoxicidade mediada por NMDAR e pela melhora na plasticidade sináptica e também, pelo efeito anti-inflamatório do composto em córtex cerebral de camundongos submetidos ao modelo de estilo de vida. Por último, no artigo 3 foi demonstrado que o (m-CF3-PhSe)2 reverteu o acúmulo de tecido adiposo abdominal relativo ao peso corporal acompanhado de lipotoxicidade hepática. Além disso, no artigo 3 o (m-CF3-PhSe)2 modulou marcadores da via glicolítica e da sinalização da insulina no fígado e neutralizou a inflamação hipotalâmica em camundongos jovens submetidos ao modelo de estilo de vida. Ainda, no artigo 3, o (m-CF3- PhSe)2 modulou os níveis de receptores de insulina, grelina e leptina no hipotálamo de camundongos jovens expostos ao modelo de estilo de vida. Em conjunto, os resultados obtidos nesta tese contribuíram para o melhor entendimento da ação do (m-CF3-PhSe)2 frente ao fenótipo do tipo depressivo, do tipo ansioso, bem como, sobre a lipotoxicidade, a sinalização de insulina e marcadores da via glicolítica no fígado e a neuroinflamação hipotalâmica induzidos pelo modelo de estilo de vida em camundongos jovens.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/openAccessSelênioEtanolDietaDepressãoAnsiedadeMetabolismoSeleniumEthanolDietDepressionAnxietyMetabolismCNPQ::CIENCIAS BIOLOGICAS::BIOQUIMICAAlterações comportamentais e metabólicas induzidas pelo estilo de vida: ação do disseleneto de m-trifluormetil-difenila em camundongosBehavioral and metabolic changes induced by lifestyle: m-trifluoromethyl-diphenyl diselenide action in miceinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/doctoralThesisNogueira, Cristina Waynehttp://lattes.cnpq.br/2877042401245169Furian, Ana FláviaBem, Andreza Fabro deVinadé, Lucia Helena do CantoBast, Rachel Krolow Santos Silvahttp://lattes.cnpq.br/5144322663312183Müller, Sabrina Grendene2008000000026006006006006006006000186436d-f662-4a5e-b36e-8c8ab8e10bf82bcbf302-a833-432e-83cd-caf84aabba72e6900342-97ef-4bb8-a11a-5b60f732af6e9f3ecc6f-2c96-4fbf-8f4f-9d159006139883066197-b48d-4585-9693-f11ab0517bcb5d5cbd5a-3393-4e01-b898-e66966d84b1areponame:Manancial - Repositório Digital da UFSMinstname:Universidade Federal de Santa Maria (UFSM)instacron:UFSMORIGINALTES_PPGCBBT_2023_MULLER_SABRINA.pdfTES_PPGCBBT_2023_MULLER_SABRINA.pdfTese de Doutoradoapplication/pdf18987719http://repositorio.ufsm.br/bitstream/1/28890/1/TES_PPGCBBT_2023_MULLER_SABRINA.pdf0b9c573b6ae99c8623eaf92dc2da9625MD51CC-LICENSElicense_rdflicense_rdfapplication/rdf+xml; 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dc.title.por.fl_str_mv |
Alterações comportamentais e metabólicas induzidas pelo estilo de vida: ação do disseleneto de m-trifluormetil-difenila em camundongos |
dc.title.alternative.eng.fl_str_mv |
Behavioral and metabolic changes induced by lifestyle: m-trifluoromethyl-diphenyl diselenide action in mice |
title |
Alterações comportamentais e metabólicas induzidas pelo estilo de vida: ação do disseleneto de m-trifluormetil-difenila em camundongos |
spellingShingle |
Alterações comportamentais e metabólicas induzidas pelo estilo de vida: ação do disseleneto de m-trifluormetil-difenila em camundongos Müller, Sabrina Grendene Selênio Etanol Dieta Depressão Ansiedade Metabolismo Selenium Ethanol Diet Depression Anxiety Metabolism CNPQ::CIENCIAS BIOLOGICAS::BIOQUIMICA |
title_short |
Alterações comportamentais e metabólicas induzidas pelo estilo de vida: ação do disseleneto de m-trifluormetil-difenila em camundongos |
title_full |
Alterações comportamentais e metabólicas induzidas pelo estilo de vida: ação do disseleneto de m-trifluormetil-difenila em camundongos |
title_fullStr |
Alterações comportamentais e metabólicas induzidas pelo estilo de vida: ação do disseleneto de m-trifluormetil-difenila em camundongos |
title_full_unstemmed |
Alterações comportamentais e metabólicas induzidas pelo estilo de vida: ação do disseleneto de m-trifluormetil-difenila em camundongos |
title_sort |
Alterações comportamentais e metabólicas induzidas pelo estilo de vida: ação do disseleneto de m-trifluormetil-difenila em camundongos |
author |
Müller, Sabrina Grendene |
author_facet |
Müller, Sabrina Grendene |
author_role |
author |
dc.contributor.advisor1.fl_str_mv |
Nogueira, Cristina Wayne |
dc.contributor.advisor1Lattes.fl_str_mv |
http://lattes.cnpq.br/2877042401245169 |
dc.contributor.referee1.fl_str_mv |
Furian, Ana Flávia |
dc.contributor.referee2.fl_str_mv |
Bem, Andreza Fabro de |
dc.contributor.referee3.fl_str_mv |
Vinadé, Lucia Helena do Canto |
dc.contributor.referee4.fl_str_mv |
Bast, Rachel Krolow Santos Silva |
dc.contributor.authorLattes.fl_str_mv |
http://lattes.cnpq.br/5144322663312183 |
dc.contributor.author.fl_str_mv |
Müller, Sabrina Grendene |
contributor_str_mv |
Nogueira, Cristina Wayne Furian, Ana Flávia Bem, Andreza Fabro de Vinadé, Lucia Helena do Canto Bast, Rachel Krolow Santos Silva |
dc.subject.por.fl_str_mv |
Selênio Etanol Dieta Depressão Ansiedade Metabolismo |
topic |
Selênio Etanol Dieta Depressão Ansiedade Metabolismo Selenium Ethanol Diet Depression Anxiety Metabolism CNPQ::CIENCIAS BIOLOGICAS::BIOQUIMICA |
dc.subject.eng.fl_str_mv |
Selenium Ethanol Diet Depression Anxiety Metabolism |
dc.subject.cnpq.fl_str_mv |
CNPQ::CIENCIAS BIOLOGICAS::BIOQUIMICA |
description |
Modern lifestyle is composed of unhealthy habits, including energy-dense food and ethanol intake. The increase in these habits has been related to depression, anxiety, and obesity. Besides, pharmacological approaches are needed to treat lifestyle-related diseases. m-Trifluoromethyldiphenyl diselenide [(m-CF3-PhSe)2] is a low-toxicity compound with pharmacological properties, including anti-inflammatory, antidepressive- and anxiolytic-like in animal models. This thesis aimed to evaluate (m-CF3-PhSe)2 effects on depressive and anxiolytic-like phenotypes and markers of metabolism of carbohydrates and lipids in young mice exposed to a lifestyle model: association of an energy-dense diet and ethanol sporadic intake. Firstly, for article 1, article 2 and article 3 25 days old Swiss male mice (CEUA: 7141061018 e 4849060420) were exposed to an energy-dense diet until postnatal day 66. From the postnatal day 45 to 60, the animals received, by the intragastric (i.g) route, an ethanol sporadic regimen, 3 times a week at 2g/kg. Posteriorly, (m-CF3-PhSe)2 was administered via i.g. for 7 days. From postnatal days 67 to 68, some animals were subjected to behavioral tests predictive of depressive-like behavior (article 1), whereas others performed anxiety-like tests (article 2). On day 69, the animals were euthanized and the cerebral cortex (article 1 and article 2), the liver, the blood, and the hypothalamus (article 3) were collected for analyses. The results of article 1 demonstrated that the modulation of the opioid system and the antioxidant effect in the cerebral cortex of mice contributed to the (m-CF3-PhSe)2 effectiveness in the lifestyle depression-induced model. In article 2, the results revealed that (m-CF3-PhSe)2 elicited an anxiolytic-like effect associated with the modulation of NMDAR-mediated neurotoxicity, neuroinflammation and by the improvement of synaptic plasticity in the cerebral cortex of mice exposed to the lifestyle model. Finally, (m-CF3-PhSe)2 reversed the accumulation of relative abdominal white adipose tissue to body weight, which was accompanied by hepatic lipotoxicity (article 3). Furthermore, (m-CF3-PhSe)2 modulated glycolytic pathway markers, hepatic insulin signaling, and counteracted hypothalamic inflammation in young mice subjected to the lifestyle-induced model. Besides, in article 3, (m-CF3-PhSe)2 modulated hypothalamic insulin, ghrelin, and leptin receptor levels of mice exposed to the lifestyle model. The results of this thesis contributed to a better comprehension of (m-CF3-PhSe)2 action against depressive- and anxiety-like phenotypes and against the lipotoxicity, insulin signaling, and glycolytic pathway markers in the liver and the hypothalamic inflammation induced by the lifestyle model in young mice. |
publishDate |
2023 |
dc.date.accessioned.fl_str_mv |
2023-05-02T14:53:37Z |
dc.date.available.fl_str_mv |
2023-05-02T14:53:37Z |
dc.date.issued.fl_str_mv |
2023-03-24 |
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/1/28890 |
url |
http://repositorio.ufsm.br/handle/1/28890 |
dc.language.iso.fl_str_mv |
por |
language |
por |
dc.relation.cnpq.fl_str_mv |
200800000002 |
dc.relation.confidence.fl_str_mv |
600 600 600 600 600 600 600 |
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) |
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UFSM |
institution |
UFSM |
reponame_str |
Manancial - Repositório Digital da UFSM |
collection |
Manancial - Repositório Digital da UFSM |
bitstream.url.fl_str_mv |
http://repositorio.ufsm.br/bitstream/1/28890/1/TES_PPGCBBT_2023_MULLER_SABRINA.pdf http://repositorio.ufsm.br/bitstream/1/28890/2/license_rdf http://repositorio.ufsm.br/bitstream/1/28890/3/license.txt |
bitstream.checksum.fl_str_mv |
0b9c573b6ae99c8623eaf92dc2da9625 4460e5956bc1d1639be9ae6146a50347 2f0571ecee68693bd5cd3f17c1e075df |
bitstream.checksumAlgorithm.fl_str_mv |
MD5 MD5 MD5 |
repository.name.fl_str_mv |
Manancial - Repositório Digital da UFSM - Universidade Federal de Santa Maria (UFSM) |
repository.mail.fl_str_mv |
|
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1794524304087449600 |