Contribuição do sistema colinérgico e da sinalização do NRF2/HO-1 para a ação anti-amnésica do 7-flúor-1,3- difenilisoquinolina-1-amina em camundongos
Ano de defesa: | 2019 |
---|---|
Autor(a) principal: | |
Orientador(a): | |
Banca de defesa: | , |
Tipo de documento: | Dissertação |
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/1/21403 |
Resumo: | Dementia is a heterogenic condition characterized by different symptoms and theories about its pathogenesis, which results in difficult to understand and in the treatment of this disease. The 7-fluoro-1,3-diphenylisoquinoline-1-amine (FDPI) have been studied due to its multitarget properties, highlighting the modulation of GABAérgic and glutamatergic systems, antioxidant and anti-inflammatory. The Nuclear factor erythroid 2-related factor 2 (Nrf2), an important tool for cellular protection, regulates the transcription of antioxidant and cytoprotective genes. On the other hand, cholinergic system is responsible for modulation of important physiologic process, such as: stress response, attention, learning and memory. Thereby, the purpose of this study was to investigate the contribution of the cholinergic system and Nrf2/ Heme oxygenase (HO-1) signaling to the potential effect of FDPI on scopolamine-induced amnesia in mice (6835140116). Adult male Swiss mice received FDPI for 5 days (5, 10 e 25 mg/kg, i.g.), from day 3 to 5 the animals received scopolamine (1mg/kg, i.p.). The results demonstrated that the FDPI administration (10 and 25 mg/kg, i.g.) was effective to reverse the scopolamine-induced amnesia in the object recognition tests. The FDPI anti-amnesic effects seem to be related to the cholinergic system through the reestablishment of AChE levels and activity increased by scopolamine in the prefrontal cortex and hippocampus of mice. In addition, FDPI restored the M1 receptor levels decreased by scopolamine in both prefrontal cortex and hippocampus of mice. Scopolamine altered oxidative stress parameters differently in the prefrontal cortex and hippocampus of mice. Whereas the prefrontal cortex was susceptible to oxidative stress, none of the parameters evaluated was altered in the hippocampus. FDPI was effective in reversing scopolamine-enhanced oxidative stress parameters as well as the alterations in Nrf2/HO-1 signaling in the prefrontal cortex of mice. Taken together, the correlation results demonstrate the contribution of the cholinergic system, oxidative stress and Nrf2/HO-1 signaling to the effect of the FDPI in the object recognition tests. |
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2021-07-13T11:15:39Z2021-07-13T11:15:39Z2019-07-26http://repositorio.ufsm.br/handle/1/21403Dementia is a heterogenic condition characterized by different symptoms and theories about its pathogenesis, which results in difficult to understand and in the treatment of this disease. The 7-fluoro-1,3-diphenylisoquinoline-1-amine (FDPI) have been studied due to its multitarget properties, highlighting the modulation of GABAérgic and glutamatergic systems, antioxidant and anti-inflammatory. The Nuclear factor erythroid 2-related factor 2 (Nrf2), an important tool for cellular protection, regulates the transcription of antioxidant and cytoprotective genes. On the other hand, cholinergic system is responsible for modulation of important physiologic process, such as: stress response, attention, learning and memory. Thereby, the purpose of this study was to investigate the contribution of the cholinergic system and Nrf2/ Heme oxygenase (HO-1) signaling to the potential effect of FDPI on scopolamine-induced amnesia in mice (6835140116). Adult male Swiss mice received FDPI for 5 days (5, 10 e 25 mg/kg, i.g.), from day 3 to 5 the animals received scopolamine (1mg/kg, i.p.). The results demonstrated that the FDPI administration (10 and 25 mg/kg, i.g.) was effective to reverse the scopolamine-induced amnesia in the object recognition tests. The FDPI anti-amnesic effects seem to be related to the cholinergic system through the reestablishment of AChE levels and activity increased by scopolamine in the prefrontal cortex and hippocampus of mice. In addition, FDPI restored the M1 receptor levels decreased by scopolamine in both prefrontal cortex and hippocampus of mice. Scopolamine altered oxidative stress parameters differently in the prefrontal cortex and hippocampus of mice. Whereas the prefrontal cortex was susceptible to oxidative stress, none of the parameters evaluated was altered in the hippocampus. FDPI was effective in reversing scopolamine-enhanced oxidative stress parameters as well as the alterations in Nrf2/HO-1 signaling in the prefrontal cortex of mice. Taken together, the correlation results demonstrate the contribution of the cholinergic system, oxidative stress and Nrf2/HO-1 signaling to the effect of the FDPI in the object recognition tests.A demência é uma condição heterogênea caracterizada por diferentes sintomas e teorias acerca da sua patogênese, o que acarreta no parco entendimento da mesma e do seu tratamento. O 7-flúor-1,3- difenilisoquinolina-1-amina (FDPI) tem sido estudado devido aos efeitos multi-alvo, como, a modulação dos sistemas GABAérgico e glutamatérgico, e pelos efeitos antioxidantes e anti-inflamatórios. O “Nuclear factor erythroid 2-related factor 2” (Nrf2) é responsável pela regulação da transcrição de genes antioxidantes e citoprotetores, sendo assim, uma importante ferramenta de proteção celular. Por outro lado, a transmissão colinérgica é responsável por modular processos fisiológicos importantes, tais como: a resposta ao estresse, a atenção, o aprendizado e a memória. Deste modo, o objetivo do presente trabalho foi investigar a contribuição do sistema colinérgico e da sinalização Nrf2/ Hemeoxigenase-1 (HO-1) para o potencial efeito anti-amnésico do FDPI no modelo induzido por escopolamina em camundongos (6835140116). Camundongos Swiss machos adultos receberam FDPI por 5 dias (5, 10 e 25 mg/kg, i.g.) e a partir do dia 3, os animais receberam escopolamina (1 mg/kg, i.p.). Os resultados demonstraram que a administração de FDPI (10 e 25 mg/kg, i.g.) foi efetiva em reverter a amnésia induzida pela escopolamina nos testes de reconhecimento do objeto. O efeito anti-amnésico do FDPI está de alguma forma relacionado a modulação do sistema colinérgico devido ao reestabelecimento da atividade e dos níveis da enzima acetilcolinesterase (AChE), aumentados pela escopolamina em córtex pré-frontal e hipocampo de camundongos. Além disso, O FDPI restaurou os níveis do receptor muscarínico M1 diminuídos pela escopolamina tanto em córtex pré-frontal como no hipocampo de camundongos. A escopolamina alterou os parâmetros de estresse oxidativo de maneira diferente no córtex pré-frontal e no hipocampo. Enquanto o córtex pré-frontal foi susceptível ao estresse, os parâmetros de hipocampo não foram alterados. O FDPI foi efetivo em reverter os parâmetros de estresse oxidativo aumentados pela escopolamina, bem como, as alterações na sinalização do Nrf2 / HO-1 em córtex pré-frontal de camundongos. Em conjunto, os presentes resultados demonstraram a contribuição do sistema colinérgico, do estresse oxidativo e da sinalização Nrf2/HO-1 para o efeito do FDPI frente aos testes comportamentais de reconhecimento do objeto.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/openAccessAmnesiaEscopolaminaIsoquinolinaNrf2/HO-1Sistema colinérgicoEstresse oxidativoScopolamineIisoquinolineCholinergicOxidative stressCNPQ::CIENCIAS BIOLOGICAS::BIOQUIMICAContribuição do sistema colinérgico e da sinalização do NRF2/HO-1 para a ação anti-amnésica do 7-flúor-1,3- difenilisoquinolina-1-amina em camundongosContribution of cholinergic system and NRF2/HO-1 signaling to the anti-amnesic action of 7-fluoro-1,3-diphenylisoquinoline-1-amine in miceinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesisNogueira, Cristina Waynehttp://lattes.cnpq.br/2877042401245169Cadoná, Francine CarlaChagas, Pietro Mariahttp://lattes.cnpq.br/5144322663312183Müller, Sabrina Grendene2008000000026006006006006000186436d-f662-4a5e-b36e-8c8ab8e10bf82bcbf302-a833-432e-83cd-caf84aabba7290dc90af-b4c9-427a-8743-532a60806ffdd6a231cf-3476-49eb-9fb6-7dad30032ddereponame:Biblioteca Digital de Teses e Dissertações do UFSMinstname:Universidade Federal de Santa Maria (UFSM)instacron:UFSMORIGINALDIS_PPGCBBT_2019_MULLER_SABRINA.pdfDIS_PPGCBBT_2019_MULLER_SABRINA.pdfDissertaçãoapplication/pdf2093269http://repositorio.ufsm.br/bitstream/1/21403/1/DIS_PPGCBBT_2019_MULLER_SABRINA.pdf7f0c3f9bbfad72b94745054e89d0681aMD51CC-LICENSElicense_rdflicense_rdfapplication/rdf+xml; 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dc.title.por.fl_str_mv |
Contribuição do sistema colinérgico e da sinalização do NRF2/HO-1 para a ação anti-amnésica do 7-flúor-1,3- difenilisoquinolina-1-amina em camundongos |
dc.title.alternative.eng.fl_str_mv |
Contribution of cholinergic system and NRF2/HO-1 signaling to the anti-amnesic action of 7-fluoro-1,3-diphenylisoquinoline-1-amine in mice |
title |
Contribuição do sistema colinérgico e da sinalização do NRF2/HO-1 para a ação anti-amnésica do 7-flúor-1,3- difenilisoquinolina-1-amina em camundongos |
spellingShingle |
Contribuição do sistema colinérgico e da sinalização do NRF2/HO-1 para a ação anti-amnésica do 7-flúor-1,3- difenilisoquinolina-1-amina em camundongos Müller, Sabrina Grendene Amnesia Escopolamina Isoquinolina Nrf2/HO-1 Sistema colinérgico Estresse oxidativo Scopolamine Iisoquinoline Cholinergic Oxidative stress CNPQ::CIENCIAS BIOLOGICAS::BIOQUIMICA |
title_short |
Contribuição do sistema colinérgico e da sinalização do NRF2/HO-1 para a ação anti-amnésica do 7-flúor-1,3- difenilisoquinolina-1-amina em camundongos |
title_full |
Contribuição do sistema colinérgico e da sinalização do NRF2/HO-1 para a ação anti-amnésica do 7-flúor-1,3- difenilisoquinolina-1-amina em camundongos |
title_fullStr |
Contribuição do sistema colinérgico e da sinalização do NRF2/HO-1 para a ação anti-amnésica do 7-flúor-1,3- difenilisoquinolina-1-amina em camundongos |
title_full_unstemmed |
Contribuição do sistema colinérgico e da sinalização do NRF2/HO-1 para a ação anti-amnésica do 7-flúor-1,3- difenilisoquinolina-1-amina em camundongos |
title_sort |
Contribuição do sistema colinérgico e da sinalização do NRF2/HO-1 para a ação anti-amnésica do 7-flúor-1,3- difenilisoquinolina-1-amina 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 |
Cadoná, Francine Carla |
dc.contributor.referee2.fl_str_mv |
Chagas, Pietro Maria |
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 Cadoná, Francine Carla Chagas, Pietro Maria |
dc.subject.por.fl_str_mv |
Amnesia Escopolamina Isoquinolina Nrf2/HO-1 Sistema colinérgico Estresse oxidativo |
topic |
Amnesia Escopolamina Isoquinolina Nrf2/HO-1 Sistema colinérgico Estresse oxidativo Scopolamine Iisoquinoline Cholinergic Oxidative stress CNPQ::CIENCIAS BIOLOGICAS::BIOQUIMICA |
dc.subject.eng.fl_str_mv |
Scopolamine Iisoquinoline Cholinergic Oxidative stress |
dc.subject.cnpq.fl_str_mv |
CNPQ::CIENCIAS BIOLOGICAS::BIOQUIMICA |
description |
Dementia is a heterogenic condition characterized by different symptoms and theories about its pathogenesis, which results in difficult to understand and in the treatment of this disease. The 7-fluoro-1,3-diphenylisoquinoline-1-amine (FDPI) have been studied due to its multitarget properties, highlighting the modulation of GABAérgic and glutamatergic systems, antioxidant and anti-inflammatory. The Nuclear factor erythroid 2-related factor 2 (Nrf2), an important tool for cellular protection, regulates the transcription of antioxidant and cytoprotective genes. On the other hand, cholinergic system is responsible for modulation of important physiologic process, such as: stress response, attention, learning and memory. Thereby, the purpose of this study was to investigate the contribution of the cholinergic system and Nrf2/ Heme oxygenase (HO-1) signaling to the potential effect of FDPI on scopolamine-induced amnesia in mice (6835140116). Adult male Swiss mice received FDPI for 5 days (5, 10 e 25 mg/kg, i.g.), from day 3 to 5 the animals received scopolamine (1mg/kg, i.p.). The results demonstrated that the FDPI administration (10 and 25 mg/kg, i.g.) was effective to reverse the scopolamine-induced amnesia in the object recognition tests. The FDPI anti-amnesic effects seem to be related to the cholinergic system through the reestablishment of AChE levels and activity increased by scopolamine in the prefrontal cortex and hippocampus of mice. In addition, FDPI restored the M1 receptor levels decreased by scopolamine in both prefrontal cortex and hippocampus of mice. Scopolamine altered oxidative stress parameters differently in the prefrontal cortex and hippocampus of mice. Whereas the prefrontal cortex was susceptible to oxidative stress, none of the parameters evaluated was altered in the hippocampus. FDPI was effective in reversing scopolamine-enhanced oxidative stress parameters as well as the alterations in Nrf2/HO-1 signaling in the prefrontal cortex of mice. Taken together, the correlation results demonstrate the contribution of the cholinergic system, oxidative stress and Nrf2/HO-1 signaling to the effect of the FDPI in the object recognition tests. |
publishDate |
2019 |
dc.date.issued.fl_str_mv |
2019-07-26 |
dc.date.accessioned.fl_str_mv |
2021-07-13T11:15:39Z |
dc.date.available.fl_str_mv |
2021-07-13T11:15:39Z |
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info:eu-repo/semantics/publishedVersion |
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info:eu-repo/semantics/masterThesis |
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masterThesis |
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publishedVersion |
dc.identifier.uri.fl_str_mv |
http://repositorio.ufsm.br/handle/1/21403 |
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http://repositorio.ufsm.br/handle/1/21403 |
dc.language.iso.fl_str_mv |
por |
language |
por |
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200800000002 |
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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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