O envolvimento de proteínas quinases na facilitação do aprendizado espacial induzido por creatina
Ano de defesa: | 2009 |
---|---|
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
|
Programa de Pós-Graduação: |
Programa de Pós-Graduação em Farmacologia
|
Departamento: |
Farmacologia
|
País: |
BR
|
Palavras-chave em Português: | |
Palavras-chave em Inglês: | |
Área do conhecimento CNPq: | |
Link de acesso: | http://repositorio.ufsm.br/handle/1/8942 |
Resumo: | Decline cognitive related to neurodegenerative diseases are very commom in patients, probably in function of aging. Since there are few effectives therapeutics approaches to loss memory treatment, but studies about new therapeutics approaches are necessary regarding neuroprotective drugs. Thus, recent works have been showing the efficacy of some neuroprotective compounds like creatine (Cr) in treatment of patients and experimental models with memory defcit. Creatine is a guanidine compound synthesized from glycine, arginine and S-adenosylmethionine in the kidneys, liver and brain that have been presented neuroprotective and neuromodulatory effect in the central nervous systems. Some works suggest that guanidine compounds like Cr could enhance learning by modulation polyamines binding sites at the N-methyl-D-Aspartate (NMDA) receptor and act as energetic buffer intracellular. In these context, the propose of this work was investigate the involvement of Cr transporter (CreaT), cAMP-dependent protein kinase A (PKA) and Ca2+/ calmodulin-dependent protein kinase II (CaMKII) signaling pathway in the spatial learning after intrahippocampal injection of Cr. After training on Barnes Maze, Cr and/or 3-GPA (inhibitor CreaT), Cr and/or H-89 (PKA inhibitor), Cr and/or STO-609, (inhibitor of CaMKII) bilateral intrahipocappus administration was performed. The results showed that intrahippocampal administration of 3-GPA, H-89 and STO-609 attenuated the facilitatory effect of Cr on spatial learnig performed on barnes Maze. Therefore, we decide investigate the involvement of the PKA (pPKA), CaMKII (pCaMKII) and CREB (pCREB) activation after intrahippocampus creatine administration in rats trained on Barnes Maze. The results showed that Cr enhanced pCREB levels and pCaMKII levels. Thirty minutes after creatine administration was observed pCREB an pCaMKII levels enhancement, on the other hand, pPKA levels enhancement was not observed. These data suggest that spatial learning enhancement elicited by Cr may be mediated by trans-cellular creatine transports, as well, CaMKII/CREB intracellular pathway in rat hippocampus |
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2010-02-102010-02-102009-11-20SOUZA, Mauren Assis de. The involvement of protein kinases on spatial learning enhancement induced by creatine. 2009. 122 f. Dissertação (Mestrado em Farmácia) - Universidade Federal de Santa Maria, Santa Maria, 2009.http://repositorio.ufsm.br/handle/1/8942Decline cognitive related to neurodegenerative diseases are very commom in patients, probably in function of aging. Since there are few effectives therapeutics approaches to loss memory treatment, but studies about new therapeutics approaches are necessary regarding neuroprotective drugs. Thus, recent works have been showing the efficacy of some neuroprotective compounds like creatine (Cr) in treatment of patients and experimental models with memory defcit. Creatine is a guanidine compound synthesized from glycine, arginine and S-adenosylmethionine in the kidneys, liver and brain that have been presented neuroprotective and neuromodulatory effect in the central nervous systems. Some works suggest that guanidine compounds like Cr could enhance learning by modulation polyamines binding sites at the N-methyl-D-Aspartate (NMDA) receptor and act as energetic buffer intracellular. In these context, the propose of this work was investigate the involvement of Cr transporter (CreaT), cAMP-dependent protein kinase A (PKA) and Ca2+/ calmodulin-dependent protein kinase II (CaMKII) signaling pathway in the spatial learning after intrahippocampal injection of Cr. After training on Barnes Maze, Cr and/or 3-GPA (inhibitor CreaT), Cr and/or H-89 (PKA inhibitor), Cr and/or STO-609, (inhibitor of CaMKII) bilateral intrahipocappus administration was performed. The results showed that intrahippocampal administration of 3-GPA, H-89 and STO-609 attenuated the facilitatory effect of Cr on spatial learnig performed on barnes Maze. Therefore, we decide investigate the involvement of the PKA (pPKA), CaMKII (pCaMKII) and CREB (pCREB) activation after intrahippocampus creatine administration in rats trained on Barnes Maze. The results showed that Cr enhanced pCREB levels and pCaMKII levels. Thirty minutes after creatine administration was observed pCREB an pCaMKII levels enhancement, on the other hand, pPKA levels enhancement was not observed. These data suggest that spatial learning enhancement elicited by Cr may be mediated by trans-cellular creatine transports, as well, CaMKII/CREB intracellular pathway in rat hippocampusO declínio cognitivo associado a doenças neurodegenerativas é um sintoma cada vez mais comum encontrado em pacientes, provavelmente devido ao aumento da expectativa de vida da população. Dada a escassez de medidas terapêuticas efetivas para o déficit de memória apresentado por pacientes, evidencia-se a importância da busca de novos compostos e do estudo de seus mecanismos de ação. Nesse contexto, recentes estudos mostraram a eficácia de algumas substâncias com ação neuroprotetora, como a creatina (Cr), na terapia de pacientes com déficit de memória e em modelos experimentais. A Cr é um composto guanidínico sintetizado endogenamente nos rins, fígado, pâncreas e cérebro, que apresenta ação neuroprotetora e neuromoduladora no sistema nervoso central. Estudos mostram que a administração de compostos guanidínicos, como a Cr, podem estar relacionados com a melhora da memória devido à interação com o sítio das poliaminas no receptor N-metil-D-Aspartato (NMDA) e por atuar como tampão energético intracelular. Neste contexto, o objetivo deste estudo foi investigar o envolvimento do transportador de Cr (CreaT), das proteínas quinases dependente de AMPc (PKA) e dependente de Ca2+/calmodulina II (CaMKII) na melhora do aprendizado espacial induzido por Cr no hipocampo de ratos. Após o treino no labirinto de Barnes, os ratos foram injetados no hipocampo, bilateralmente, com Cr e/ou 3-ácido guanidinico propiônico (3-GPA, um inibidor do transportador de creatina); Cr e/ou [N-[2-(p-Bromocinnamylamino)ethyl]-5-isoquinoline sulfonamide, Di-HCl Salt] (H-89, um inibidor da PKA); Cr e/ou 1,8-Naphthoylene benzimidazole-3- carboxylic acid (STO-609, um inibidor da CaMKII). A administração de 3-GPA, H-89 e STO-609 diminuiu o efeito facilitatório da Cr na memória espacial de ratos, observado no teste do labirinto de Barnes. De acordo com esses resultados, decidimos investigar o envolvimento da ativação do elemento de ligação responsivo ao AMPc (pCREB), PKA (pPKA) e CaMKII (pCaMKII) após a administração de Cr no hipocampo de animais treinados no labirinto de Barnes. Trinta minutos após a injeção de Cr, foi observado um aumento nos níveis de pCREB e pCaMKII, mas não nos níveis de pPKA no hipocampo de ratos. Estes achados sugerem que a facilitação do aprendizado espacial induzido pela Cr depende do seu transporte para o meio intracelular, assim como, envolve a via de sinalização celular da CaMKII/CREB no hipocampo de ratos.Coordenação de Aperfeiçoamento de Pessoal de Nível Superiorapplication/pdfporUniversidade Federal de Santa MariaPrograma de Pós-Graduação em FarmacologiaUFSMBRFarmacologiaMemória espacialLabirinto de BarnesCreatinaProteínas quinasesSpatial learningBarnes mazeCreatineProtein kinaseCNPQ::CIENCIAS BIOLOGICAS::FARMACOLOGIAO envolvimento de proteínas quinases na facilitação do aprendizado espacial induzido por creatinaThe involvement of protein kinases on spatial learning enhancement induced by creatineinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesisFighera, Michele Rechiahttp://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4762398D8Rubin, Maribel Antonellohttp://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4794806H7Nogueira, Cristina Waynehttp://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4728219Y9http://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4215645E1Souza, Mauren Assis de2010000000004005005005005008306e5eb-747a-45a0-a023-955603a45dcdafccab86-4fac-4aff-bd5c-6197f678f41d54e815ae-8af3-4abc-8a86-fc8ea077520b03fcea4e-532c-4289-b5c0-2e0fe6d48c48info:eu-repo/semantics/openAccessreponame:Biblioteca Digital de Teses e Dissertações do UFSMinstname:Universidade Federal de Santa Maria (UFSM)instacron:UFSMORIGINALSOUZA, MAUREN ASSIS DE.pdfapplication/pdf2165076http://repositorio.ufsm.br/bitstream/1/8942/1/SOUZA%2c%20MAUREN%20ASSIS%20DE.pdfeb4d35d6f076bafe154c884fed0d0908MD51TEXTSOUZA, MAUREN ASSIS DE.pdf.txtSOUZA, MAUREN ASSIS DE.pdf.txtExtracted texttext/plain201939http://repositorio.ufsm.br/bitstream/1/8942/2/SOUZA%2c%20MAUREN%20ASSIS%20DE.pdf.txtfc1861b54a7929c16285dbed7f976f89MD52THUMBNAILSOUZA, MAUREN ASSIS DE.pdf.jpgSOUZA, MAUREN ASSIS DE.pdf.jpgIM Thumbnailimage/jpeg5753http://repositorio.ufsm.br/bitstream/1/8942/3/SOUZA%2c%20MAUREN%20ASSIS%20DE.pdf.jpgca1e119ed1cb036039f84796e1d3b75dMD531/89422017-07-25 11:49:59.301oai:repositorio.ufsm.br:1/8942Biblioteca Digital de Teses e Dissertaçõeshttps://repositorio.ufsm.br/ONGhttps://repositorio.ufsm.br/oai/requestatendimento.sib@ufsm.br||tedebc@gmail.comopendoar:2017-07-25T14:49:59Biblioteca Digital de Teses e Dissertações do UFSM - Universidade Federal de Santa Maria (UFSM)false |
dc.title.por.fl_str_mv |
O envolvimento de proteínas quinases na facilitação do aprendizado espacial induzido por creatina |
dc.title.alternative.eng.fl_str_mv |
The involvement of protein kinases on spatial learning enhancement induced by creatine |
title |
O envolvimento de proteínas quinases na facilitação do aprendizado espacial induzido por creatina |
spellingShingle |
O envolvimento de proteínas quinases na facilitação do aprendizado espacial induzido por creatina Souza, Mauren Assis de Memória espacial Labirinto de Barnes Creatina Proteínas quinases Spatial learning Barnes maze Creatine Protein kinase CNPQ::CIENCIAS BIOLOGICAS::FARMACOLOGIA |
title_short |
O envolvimento de proteínas quinases na facilitação do aprendizado espacial induzido por creatina |
title_full |
O envolvimento de proteínas quinases na facilitação do aprendizado espacial induzido por creatina |
title_fullStr |
O envolvimento de proteínas quinases na facilitação do aprendizado espacial induzido por creatina |
title_full_unstemmed |
O envolvimento de proteínas quinases na facilitação do aprendizado espacial induzido por creatina |
title_sort |
O envolvimento de proteínas quinases na facilitação do aprendizado espacial induzido por creatina |
author |
Souza, Mauren Assis de |
author_facet |
Souza, Mauren Assis de |
author_role |
author |
dc.contributor.advisor1.fl_str_mv |
Fighera, Michele Rechia |
dc.contributor.advisor1Lattes.fl_str_mv |
http://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4762398D8 |
dc.contributor.referee1.fl_str_mv |
Rubin, Maribel Antonello |
dc.contributor.referee1Lattes.fl_str_mv |
http://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4794806H7 |
dc.contributor.referee2.fl_str_mv |
Nogueira, Cristina Wayne |
dc.contributor.referee2Lattes.fl_str_mv |
http://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4728219Y9 |
dc.contributor.authorLattes.fl_str_mv |
http://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4215645E1 |
dc.contributor.author.fl_str_mv |
Souza, Mauren Assis de |
contributor_str_mv |
Fighera, Michele Rechia Rubin, Maribel Antonello Nogueira, Cristina Wayne |
dc.subject.por.fl_str_mv |
Memória espacial Labirinto de Barnes Creatina Proteínas quinases |
topic |
Memória espacial Labirinto de Barnes Creatina Proteínas quinases Spatial learning Barnes maze Creatine Protein kinase CNPQ::CIENCIAS BIOLOGICAS::FARMACOLOGIA |
dc.subject.eng.fl_str_mv |
Spatial learning Barnes maze Creatine Protein kinase |
dc.subject.cnpq.fl_str_mv |
CNPQ::CIENCIAS BIOLOGICAS::FARMACOLOGIA |
description |
Decline cognitive related to neurodegenerative diseases are very commom in patients, probably in function of aging. Since there are few effectives therapeutics approaches to loss memory treatment, but studies about new therapeutics approaches are necessary regarding neuroprotective drugs. Thus, recent works have been showing the efficacy of some neuroprotective compounds like creatine (Cr) in treatment of patients and experimental models with memory defcit. Creatine is a guanidine compound synthesized from glycine, arginine and S-adenosylmethionine in the kidneys, liver and brain that have been presented neuroprotective and neuromodulatory effect in the central nervous systems. Some works suggest that guanidine compounds like Cr could enhance learning by modulation polyamines binding sites at the N-methyl-D-Aspartate (NMDA) receptor and act as energetic buffer intracellular. In these context, the propose of this work was investigate the involvement of Cr transporter (CreaT), cAMP-dependent protein kinase A (PKA) and Ca2+/ calmodulin-dependent protein kinase II (CaMKII) signaling pathway in the spatial learning after intrahippocampal injection of Cr. After training on Barnes Maze, Cr and/or 3-GPA (inhibitor CreaT), Cr and/or H-89 (PKA inhibitor), Cr and/or STO-609, (inhibitor of CaMKII) bilateral intrahipocappus administration was performed. The results showed that intrahippocampal administration of 3-GPA, H-89 and STO-609 attenuated the facilitatory effect of Cr on spatial learnig performed on barnes Maze. Therefore, we decide investigate the involvement of the PKA (pPKA), CaMKII (pCaMKII) and CREB (pCREB) activation after intrahippocampus creatine administration in rats trained on Barnes Maze. The results showed that Cr enhanced pCREB levels and pCaMKII levels. Thirty minutes after creatine administration was observed pCREB an pCaMKII levels enhancement, on the other hand, pPKA levels enhancement was not observed. These data suggest that spatial learning enhancement elicited by Cr may be mediated by trans-cellular creatine transports, as well, CaMKII/CREB intracellular pathway in rat hippocampus |
publishDate |
2009 |
dc.date.issued.fl_str_mv |
2009-11-20 |
dc.date.accessioned.fl_str_mv |
2010-02-10 |
dc.date.available.fl_str_mv |
2010-02-10 |
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.citation.fl_str_mv |
SOUZA, Mauren Assis de. The involvement of protein kinases on spatial learning enhancement induced by creatine. 2009. 122 f. Dissertação (Mestrado em Farmácia) - Universidade Federal de Santa Maria, Santa Maria, 2009. |
dc.identifier.uri.fl_str_mv |
http://repositorio.ufsm.br/handle/1/8942 |
identifier_str_mv |
SOUZA, Mauren Assis de. The involvement of protein kinases on spatial learning enhancement induced by creatine. 2009. 122 f. Dissertação (Mestrado em Farmácia) - Universidade Federal de Santa Maria, Santa Maria, 2009. |
url |
http://repositorio.ufsm.br/handle/1/8942 |
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por |
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Universidade Federal de Santa Maria |
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UFSM |
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Farmacologia |
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Universidade Federal de Santa Maria |
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