Efeito neuroprotetor do exercício de natação e do disseleneto de m-trifluormetil difenila em um modelo de dieta hipercalórica em camundongos jovens
Ano de defesa: | 2021 |
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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/1/23583 |
Resumo: | The nutrition transition process has generated negative impacts on population health. The increasing consumption of foods and beverages with higher energy density and lower nutritional value promotes damage to the body, including cognitive functions. Therapeutic strategies to control and or prevent injuries induced by excessive consumption of high-calorie foods are necessary. Aerobic exercise is a non-pharmacological strategy that shows positive effects on oxidant status and cognitive function in models of neurodegenerative diseases. m-Trifluoromethyl-diphenyl diselenide (m-CF3-PhSe)2 is a low-toxicity organoselenium compound with anti-inflammatory and anti-apoptotic properties in the central nervous system. This thesis aimed to evaluate the swimming exercise and (m-CF3-PhSe)2 effects on the memory of young mice exposed to a high-calorie diet, elucidating the possible mechanisms involved in the neuroprotective action of both therapies. Initially, both in the article and manuscript male Swiss mice (21 postnatal days) were exposed to a high-calorie diet supplemented with 20% lipids + 20% carbohydrate for 28 days (CEUA: 7134140318 – 8990220420). The article results demonstrate that the moderate-intensity swimming exercise performed for 28 days protected against impairments of spatial, location, and recognition memories in young mice fed a high-calorie diet. A decrease in oxidative stress and the modulation of the Keap1/Nrf2/HO-1 pathway were found in the hippocampus of exercised mice exposed to a high-calorie diet. Swimming exercise modulated the hippocampal levels of mtTFA protein. The positive modulation of Keap1/Nrf2/HO-1 and mtTFA proteins contributed to the swimming exercise effects on behavioral memory tests. The manuscript results reveal that (m-CF3-PhSe)2, at a dose of 5 mg/kg for 7 days (intragastric route), improved location and recognition memory in young mice exposed to a high-calorie diet. (m-CF3-PhSe)2 anti-inflammatory effects were demonstrated by decreasing the hippocampal IL-1β, COX-2, and GFAP protein levels, which were increased after exposure to a high-calorie diet (m-CF3-PhSe)2 modulated the MAPK pathways by decreasing the levels of p38, JNK, and ERK phosphorylation. Besides, (m-CF3-PhSe)2 restored the increase in the levels of apoptotic proteins Bax and cleaved PARP and the decrease in the anti-apoptotic protein Bcl-2 in the hippocampus of young mice exposed to a high-calorie diet. Both therapies were effective against fatty tissue accumulation caused by exposure to a high-calorie diet. In conclusion, this thesis help to understanding how neuroprotective mechanisms contribute to swimming exercise and (m-CF3-PhSe)2 positive effects on memory of mice exposed to a high-calorie diet. Thus, both therapies are possible strategies (non-pharmacological and pharmacological) to treat memory damage caused by a high-calorie diet. |
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2022-01-19T13:57:37Z2022-01-19T13:57:37Z2021-05-21http://repositorio.ufsm.br/handle/1/23583The nutrition transition process has generated negative impacts on population health. The increasing consumption of foods and beverages with higher energy density and lower nutritional value promotes damage to the body, including cognitive functions. Therapeutic strategies to control and or prevent injuries induced by excessive consumption of high-calorie foods are necessary. Aerobic exercise is a non-pharmacological strategy that shows positive effects on oxidant status and cognitive function in models of neurodegenerative diseases. m-Trifluoromethyl-diphenyl diselenide (m-CF3-PhSe)2 is a low-toxicity organoselenium compound with anti-inflammatory and anti-apoptotic properties in the central nervous system. This thesis aimed to evaluate the swimming exercise and (m-CF3-PhSe)2 effects on the memory of young mice exposed to a high-calorie diet, elucidating the possible mechanisms involved in the neuroprotective action of both therapies. Initially, both in the article and manuscript male Swiss mice (21 postnatal days) were exposed to a high-calorie diet supplemented with 20% lipids + 20% carbohydrate for 28 days (CEUA: 7134140318 – 8990220420). The article results demonstrate that the moderate-intensity swimming exercise performed for 28 days protected against impairments of spatial, location, and recognition memories in young mice fed a high-calorie diet. A decrease in oxidative stress and the modulation of the Keap1/Nrf2/HO-1 pathway were found in the hippocampus of exercised mice exposed to a high-calorie diet. Swimming exercise modulated the hippocampal levels of mtTFA protein. The positive modulation of Keap1/Nrf2/HO-1 and mtTFA proteins contributed to the swimming exercise effects on behavioral memory tests. The manuscript results reveal that (m-CF3-PhSe)2, at a dose of 5 mg/kg for 7 days (intragastric route), improved location and recognition memory in young mice exposed to a high-calorie diet. (m-CF3-PhSe)2 anti-inflammatory effects were demonstrated by decreasing the hippocampal IL-1β, COX-2, and GFAP protein levels, which were increased after exposure to a high-calorie diet (m-CF3-PhSe)2 modulated the MAPK pathways by decreasing the levels of p38, JNK, and ERK phosphorylation. Besides, (m-CF3-PhSe)2 restored the increase in the levels of apoptotic proteins Bax and cleaved PARP and the decrease in the anti-apoptotic protein Bcl-2 in the hippocampus of young mice exposed to a high-calorie diet. Both therapies were effective against fatty tissue accumulation caused by exposure to a high-calorie diet. In conclusion, this thesis help to understanding how neuroprotective mechanisms contribute to swimming exercise and (m-CF3-PhSe)2 positive effects on memory of mice exposed to a high-calorie diet. Thus, both therapies are possible strategies (non-pharmacological and pharmacological) to treat memory damage caused by a high-calorie diet.O processo de transição nutricional tem gerado repercussões negativas na saúde populacional. O crescente aumento do consumo de alimentos e bebidas com alta densidade energética e baixo valor nutricional promove danos ao organismo, incluindo prejuízo nas funções cognitivas. Estratégias terapêuticas para controlar e/ou prevenir danos induzidos pelo consumo excessivo de alimentos hipercalóricos são necessárias. O exercício aeróbico é uma terapia não-farmacológica com ação antioxidante e efeitos na melhora da função cognitiva em modelos animais de doenças neurodegenerativas. O composto orgânico de selênio, disseleneto de m-trifluormetil-difenila) (m-CF3-PhSe)2, possui baixa toxicidade e propriedades farmacológicas, tais como anti-inflamatória e anti-apoptótica, no sistema nervoso central. Com isso, o objetivo desta tese foi avaliar os efeitos do exercício de natação e do (m-CF3-PhSe)2 sobre a aprendizagem e memória de camundongos jovens expostos a uma dieta hipercalórica, elucidando os possíveis mecanismos envolvidos em ambas as terapias. Inicialmente, tanto no artigo como no manuscrito os camundongos Swiss machos (21 dias pós-natal) foram expostos a uma dieta hipercalórica contendo a adição de 20% lipídeos + 20% carboidratos durante 28 dias de protocolo experimental (CEUA: 7134140318 – 8990220420). Os resultados do artigo demonstraram que o exercício de natação de intensidade moderada realizado durante 28 dias (5 vezes por semanda), protegeu contra os prejuízos nas memórias de localização e reconhecimento do objeto e na memória espacial em camundongos jovens alimentados com uma dieta hipercalórica. O exercício de natação demonstrou seu efeito antioxidante através da diminuição do estresse oxidativo e da modulação da via de sinalização Keap1/Nrf2/HO-1 no hipocampo dos camundongos expostos a dieta hipercalórica. Ainda, os resultados indicaram que o exercício de natação restaurou os níveis hipocampais da proteína mtTFA. A modulação positiva das proteínas Keap1/Nrf2/HO-1 e mtTFA contribuiu para os efeitos do exercício de natação sobre os testes comportamentais de aprendizagem e memória. No manuscrito, os resultados revelaram que o tratamento com (m-CF3-PhSe)2, na dose de 5 mg/kg por 7 dias (via intragástrica), apresentou efeitos positivos na melhora dos prejuízos nas memórias de localização e reconhecimento do objeto em camundongos expostos a uma dieta hipercalórica. Os efeitos anti-inflamatórios do (m-CF3-PhSe)2 foram demonstrados pela diminuição dos níveis hipocampais das proteínas IL-1β, COX-2 e GFAP, os quais foram aumentados pela exposição a dieta hipercalórica. Para complementar a ação anti-inflamatória, os resultados mostraram que a administração do (m-CF3-PhSe)2 modulou a via de sinalização das MAPKs através da diminuição da fosforilação das proteínas p38, JNK e ERK. Além disso, o composto (m-CF3-PhSe)2 reverteu o aumento dos níveis das proteínas apoptóticas Bax e PARP clivada, e a diminuição da anti-apoptótica Bcl-2 em hipocampo de camundongos jovens expostos a dieta hipercalórica. Ambas as terapias foram eficazes em proteger contra o aumento de tecido adiposo causado pela exposição à dieta. Por fim, os resultados dessa tese contribuíram para a compreensão dos mecanismos neuroprotetores pelos quais o exercício de natação e o composto (m-CF3-PhSe)2 melhoram os prejuízos de aprendizagem e memória induzidos pela exposição a uma dieta hipercalórica em camundongos jovens, sendo possíveis estratégias (não-farmacológica e farmacológica) para o tratamento destas condições.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/openAccessExercícioSelênioMemóriaEstresse oxidativoInflamaçãoApoptoseExerciseSeleniumMemoryOxidative stressInflammationApoptosisCNPQ::CIENCIAS BIOLOGICAS::BIOQUIMICAEfeito neuroprotetor do exercício de natação e do disseleneto de m-trifluormetil difenila em um modelo de dieta hipercalórica em camundongos jovensNeuroprotective effect of swimming exercise and m-trifluormethil diphenil diselenide in a hypercaloric diet model in young miceinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/doctoralThesisNogueira, Cristina Waynehttp://lattes.cnpq.br/2877042401245169Furian, Ana FláviaPase, Camila SimonettiGuerra, Gustavo PetriSpanevello, Roselia Mariahttp://lattes.cnpq.br/2146365032007195Jardim, Natália da Silva2008000000026006006006006000186436d-f662-4a5e-b36e-8c8ab8e10bf8876b9505-f503-4e74-83e1-c368a7cdbcd3e6900342-97ef-4bb8-a11a-5b60f732af6e4a585ee7-471b-4af5-8536-8d29af2f76f018d4abbf-ab76-4e90-a7cd-8b0d2fe1e83d03c79a9b-51ab-4e2d-a595-8040766e0bd5reponame:Biblioteca Digital de Teses e Dissertações do UFSMinstname:Universidade Federal de Santa Maria (UFSM)instacron:UFSMORIGINALTES_PPGBT_2021_JARDIM_NATÁLIA.pdfTES_PPGBT_2021_JARDIM_NATÁLIA.pdfTese de Doutoradoapplication/pdf25512487http://repositorio.ufsm.br/bitstream/1/23583/1/TES_PPGBT_2021_JARDIM_NAT%c3%81LIA.pdf835021eea95e7b55aa1ad5933b084a16MD51CC-LICENSElicense_rdflicense_rdfapplication/rdf+xml; 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dc.title.por.fl_str_mv |
Efeito neuroprotetor do exercício de natação e do disseleneto de m-trifluormetil difenila em um modelo de dieta hipercalórica em camundongos jovens |
dc.title.alternative.eng.fl_str_mv |
Neuroprotective effect of swimming exercise and m-trifluormethil diphenil diselenide in a hypercaloric diet model in young mice |
title |
Efeito neuroprotetor do exercício de natação e do disseleneto de m-trifluormetil difenila em um modelo de dieta hipercalórica em camundongos jovens |
spellingShingle |
Efeito neuroprotetor do exercício de natação e do disseleneto de m-trifluormetil difenila em um modelo de dieta hipercalórica em camundongos jovens Jardim, Natália da Silva Exercício Selênio Memória Estresse oxidativo Inflamação Apoptose Exercise Selenium Memory Oxidative stress Inflammation Apoptosis CNPQ::CIENCIAS BIOLOGICAS::BIOQUIMICA |
title_short |
Efeito neuroprotetor do exercício de natação e do disseleneto de m-trifluormetil difenila em um modelo de dieta hipercalórica em camundongos jovens |
title_full |
Efeito neuroprotetor do exercício de natação e do disseleneto de m-trifluormetil difenila em um modelo de dieta hipercalórica em camundongos jovens |
title_fullStr |
Efeito neuroprotetor do exercício de natação e do disseleneto de m-trifluormetil difenila em um modelo de dieta hipercalórica em camundongos jovens |
title_full_unstemmed |
Efeito neuroprotetor do exercício de natação e do disseleneto de m-trifluormetil difenila em um modelo de dieta hipercalórica em camundongos jovens |
title_sort |
Efeito neuroprotetor do exercício de natação e do disseleneto de m-trifluormetil difenila em um modelo de dieta hipercalórica em camundongos jovens |
author |
Jardim, Natália da Silva |
author_facet |
Jardim, Natália da Silva |
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 |
Pase, Camila Simonetti |
dc.contributor.referee3.fl_str_mv |
Guerra, Gustavo Petri |
dc.contributor.referee4.fl_str_mv |
Spanevello, Roselia Maria |
dc.contributor.authorLattes.fl_str_mv |
http://lattes.cnpq.br/2146365032007195 |
dc.contributor.author.fl_str_mv |
Jardim, Natália da Silva |
contributor_str_mv |
Nogueira, Cristina Wayne Furian, Ana Flávia Pase, Camila Simonetti Guerra, Gustavo Petri Spanevello, Roselia Maria |
dc.subject.por.fl_str_mv |
Exercício Selênio Memória Estresse oxidativo Inflamação Apoptose |
topic |
Exercício Selênio Memória Estresse oxidativo Inflamação Apoptose Exercise Selenium Memory Oxidative stress Inflammation Apoptosis CNPQ::CIENCIAS BIOLOGICAS::BIOQUIMICA |
dc.subject.eng.fl_str_mv |
Exercise Selenium Memory Oxidative stress Inflammation Apoptosis |
dc.subject.cnpq.fl_str_mv |
CNPQ::CIENCIAS BIOLOGICAS::BIOQUIMICA |
description |
The nutrition transition process has generated negative impacts on population health. The increasing consumption of foods and beverages with higher energy density and lower nutritional value promotes damage to the body, including cognitive functions. Therapeutic strategies to control and or prevent injuries induced by excessive consumption of high-calorie foods are necessary. Aerobic exercise is a non-pharmacological strategy that shows positive effects on oxidant status and cognitive function in models of neurodegenerative diseases. m-Trifluoromethyl-diphenyl diselenide (m-CF3-PhSe)2 is a low-toxicity organoselenium compound with anti-inflammatory and anti-apoptotic properties in the central nervous system. This thesis aimed to evaluate the swimming exercise and (m-CF3-PhSe)2 effects on the memory of young mice exposed to a high-calorie diet, elucidating the possible mechanisms involved in the neuroprotective action of both therapies. Initially, both in the article and manuscript male Swiss mice (21 postnatal days) were exposed to a high-calorie diet supplemented with 20% lipids + 20% carbohydrate for 28 days (CEUA: 7134140318 – 8990220420). The article results demonstrate that the moderate-intensity swimming exercise performed for 28 days protected against impairments of spatial, location, and recognition memories in young mice fed a high-calorie diet. A decrease in oxidative stress and the modulation of the Keap1/Nrf2/HO-1 pathway were found in the hippocampus of exercised mice exposed to a high-calorie diet. Swimming exercise modulated the hippocampal levels of mtTFA protein. The positive modulation of Keap1/Nrf2/HO-1 and mtTFA proteins contributed to the swimming exercise effects on behavioral memory tests. The manuscript results reveal that (m-CF3-PhSe)2, at a dose of 5 mg/kg for 7 days (intragastric route), improved location and recognition memory in young mice exposed to a high-calorie diet. (m-CF3-PhSe)2 anti-inflammatory effects were demonstrated by decreasing the hippocampal IL-1β, COX-2, and GFAP protein levels, which were increased after exposure to a high-calorie diet (m-CF3-PhSe)2 modulated the MAPK pathways by decreasing the levels of p38, JNK, and ERK phosphorylation. Besides, (m-CF3-PhSe)2 restored the increase in the levels of apoptotic proteins Bax and cleaved PARP and the decrease in the anti-apoptotic protein Bcl-2 in the hippocampus of young mice exposed to a high-calorie diet. Both therapies were effective against fatty tissue accumulation caused by exposure to a high-calorie diet. In conclusion, this thesis help to understanding how neuroprotective mechanisms contribute to swimming exercise and (m-CF3-PhSe)2 positive effects on memory of mice exposed to a high-calorie diet. Thus, both therapies are possible strategies (non-pharmacological and pharmacological) to treat memory damage caused by a high-calorie diet. |
publishDate |
2021 |
dc.date.issued.fl_str_mv |
2021-05-21 |
dc.date.accessioned.fl_str_mv |
2022-01-19T13:57:37Z |
dc.date.available.fl_str_mv |
2022-01-19T13:57:37Z |
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/1/23583 |
url |
http://repositorio.ufsm.br/handle/1/23583 |
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 |
dc.relation.authority.fl_str_mv |
0186436d-f662-4a5e-b36e-8c8ab8e10bf8 876b9505-f503-4e74-83e1-c368a7cdbcd3 e6900342-97ef-4bb8-a11a-5b60f732af6e 4a585ee7-471b-4af5-8536-8d29af2f76f0 18d4abbf-ab76-4e90-a7cd-8b0d2fe1e83d 03c79a9b-51ab-4e2d-a595-8040766e0bd5 |
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:Biblioteca Digital de Teses e Dissertações do 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 |
Biblioteca Digital de Teses e Dissertações do UFSM |
collection |
Biblioteca Digital de Teses e Dissertações do UFSM |
bitstream.url.fl_str_mv |
http://repositorio.ufsm.br/bitstream/1/23583/1/TES_PPGBT_2021_JARDIM_NAT%c3%81LIA.pdf http://repositorio.ufsm.br/bitstream/1/23583/2/license_rdf http://repositorio.ufsm.br/bitstream/1/23583/3/license.txt |
bitstream.checksum.fl_str_mv |
835021eea95e7b55aa1ad5933b084a16 4460e5956bc1d1639be9ae6146a50347 2f0571ecee68693bd5cd3f17c1e075df |
bitstream.checksumAlgorithm.fl_str_mv |
MD5 MD5 MD5 |
repository.name.fl_str_mv |
Biblioteca Digital de Teses e Dissertações do UFSM - Universidade Federal de Santa Maria (UFSM) |
repository.mail.fl_str_mv |
atendimento.sib@ufsm.br||tedebc@gmail.com |
_version_ |
1793240171367366656 |