Infusão intra-hipocampal de espermidina melhora a persistência da memória e a persistência da reconsolidação da memória em ratos
Ano de defesa: | 2016 |
---|---|
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/1/18049 |
Resumo: | The persistence of memory requires a delayed healing process (12-24 h after the acquisition) wherein the synthesis of new proteins and derived neurotrophic factor (BDNF), are essential. The polyamines putrescine, spermidine (SPD) and spermine, they act as endogenous modulators of various ion channels, including the glutamatergic receptor subtype N-methyl-D-aspartate (NMDAr). Systemic administration and intracerebral SPD improves memory in various tasks in rodents. It has recently been demonstrated that systemic administration of SPD improves the persistence and reconsolidation of memory in contextual fear conditioning task in rats. However, there are few studies to elucidate the mechanism of action and the brain structures involved in the effect of polyamines in these stages of memory. Therefore, the aim of this study was to evaluate the effect of intra-hippocampal infusion of SPD in the persistence of memory and the persistence of memory reconsolidation of animals subjected to contextual fear conditioning task. Also, check the involvement of NMDAr, protein synthesis and protein kinase dependent on cAMP (PKA), in the persistence of memory. We also investigated the involvement of BDNF expression and neurogenesis in persistent memory reconsolidation. Thus, adult male Wistar rats were submitted to training in contextual fear conditioning task, and 12 h post-training, received an intra-hippocampal infusion SPD (0.02-2 nmol/site), arcaine (0.02-2 nmol/site), a competitive antagonist of the polyamine NMDAr binding site as well as the protein synthesis inhibitor (anisomycin, 2-20 μg/site) and PKA inhibitor (H- 89 0.5-10 pmol/site). One group of animals was euthanized, 3 h after injection of SPD, for further evaluation of the expression of hippocampal PKA. Another group of animals was tested 2 or 7 days after training. While intra-hippocampal infusion SPD (2 nmol/site) improved the persistence of memory, arcaine (2 nmol/site) and anisomycin (20 μg/site) impaired the persistence of memory of the animals tested 7 days after training. The arcaine (0.2 nmol/ site), the anisomycin (2 μg/site) and H-89 (10 pmol/site), at doses that have no effect per se, prevented the improvement of the persistence of memory induced by SPD (2 nmol/ site). The SPD (2 nmol/site) increased the expression of phospho-PKA/total-PKA, while the H-89 (10 pmol/site) prevented the increase in phospho-PKA/total-PKA-induced SPD. In addition, we evaluated the effect of polyamines in persistent memory reconsolidation. For this, Wistar adult male rats were trained in contextual fear conditioning task, 24 h post- training memory has been reactivated, and 0, 6, 12 or 24 h post-reactivation received an intra-hippocampal infusion SPD (0.02- 2 nmol/ site). One group of animals was euthanized 3 h after injection of SPD and the hippocampus was removed for later evaluation of the expression of total and mature BDNF. Another group of animals was tested 2 or 7 days after the reactivation. The SPD (2 nmol/site) infused 0 h and 12 h post-reactivation, improved the persistence of reconsolidation of memory, only in animals tested 7 days after reactivation. Moreover, the SPD (2 nmol/site) infused 12 h after reactivation increased the expression of mature BDNF, but not the total BDNF in rat hippocampus. In vitro studies demonstrated that the SPD increased the number of neurites, migration cell and levels of BDNF in neural progenitor cells. Therefore, the present results suggest an upregulation of polyamines in hippocampal NMDAr, protein synthesis and PKA in the memory persistence phase. This study also suggests the involvement of the SPD in persistent memory reconsolidation probably through mechanism to facilitate the increase in mature hippocampal BDNF expression and neurogenesis. |
id |
UFSM_7d82659b62b931e47aed7928bafed6ee |
---|---|
oai_identifier_str |
oai:repositorio.ufsm.br:1/18049 |
network_acronym_str |
UFSM |
network_name_str |
Biblioteca Digital de Teses e Dissertações do UFSM |
repository_id_str |
|
spelling |
2019-08-28T11:03:23Z2019-08-28T11:03:23Z2016-08-19http://repositorio.ufsm.br/handle/1/18049The persistence of memory requires a delayed healing process (12-24 h after the acquisition) wherein the synthesis of new proteins and derived neurotrophic factor (BDNF), are essential. The polyamines putrescine, spermidine (SPD) and spermine, they act as endogenous modulators of various ion channels, including the glutamatergic receptor subtype N-methyl-D-aspartate (NMDAr). Systemic administration and intracerebral SPD improves memory in various tasks in rodents. It has recently been demonstrated that systemic administration of SPD improves the persistence and reconsolidation of memory in contextual fear conditioning task in rats. However, there are few studies to elucidate the mechanism of action and the brain structures involved in the effect of polyamines in these stages of memory. Therefore, the aim of this study was to evaluate the effect of intra-hippocampal infusion of SPD in the persistence of memory and the persistence of memory reconsolidation of animals subjected to contextual fear conditioning task. Also, check the involvement of NMDAr, protein synthesis and protein kinase dependent on cAMP (PKA), in the persistence of memory. We also investigated the involvement of BDNF expression and neurogenesis in persistent memory reconsolidation. Thus, adult male Wistar rats were submitted to training in contextual fear conditioning task, and 12 h post-training, received an intra-hippocampal infusion SPD (0.02-2 nmol/site), arcaine (0.02-2 nmol/site), a competitive antagonist of the polyamine NMDAr binding site as well as the protein synthesis inhibitor (anisomycin, 2-20 μg/site) and PKA inhibitor (H- 89 0.5-10 pmol/site). One group of animals was euthanized, 3 h after injection of SPD, for further evaluation of the expression of hippocampal PKA. Another group of animals was tested 2 or 7 days after training. While intra-hippocampal infusion SPD (2 nmol/site) improved the persistence of memory, arcaine (2 nmol/site) and anisomycin (20 μg/site) impaired the persistence of memory of the animals tested 7 days after training. The arcaine (0.2 nmol/ site), the anisomycin (2 μg/site) and H-89 (10 pmol/site), at doses that have no effect per se, prevented the improvement of the persistence of memory induced by SPD (2 nmol/ site). The SPD (2 nmol/site) increased the expression of phospho-PKA/total-PKA, while the H-89 (10 pmol/site) prevented the increase in phospho-PKA/total-PKA-induced SPD. In addition, we evaluated the effect of polyamines in persistent memory reconsolidation. For this, Wistar adult male rats were trained in contextual fear conditioning task, 24 h post- training memory has been reactivated, and 0, 6, 12 or 24 h post-reactivation received an intra-hippocampal infusion SPD (0.02- 2 nmol/ site). One group of animals was euthanized 3 h after injection of SPD and the hippocampus was removed for later evaluation of the expression of total and mature BDNF. Another group of animals was tested 2 or 7 days after the reactivation. The SPD (2 nmol/site) infused 0 h and 12 h post-reactivation, improved the persistence of reconsolidation of memory, only in animals tested 7 days after reactivation. Moreover, the SPD (2 nmol/site) infused 12 h after reactivation increased the expression of mature BDNF, but not the total BDNF in rat hippocampus. In vitro studies demonstrated that the SPD increased the number of neurites, migration cell and levels of BDNF in neural progenitor cells. Therefore, the present results suggest an upregulation of polyamines in hippocampal NMDAr, protein synthesis and PKA in the memory persistence phase. This study also suggests the involvement of the SPD in persistent memory reconsolidation probably through mechanism to facilitate the increase in mature hippocampal BDNF expression and neurogenesis.A persistência da memória requer um processo de consolidação tardia (12-24 h após a aquisição) na qual a síntese de novas proteínas e do fator neurotrófico derivado do encéfalo (BDNF), são essenciais. As poliaminas putrescina, espermidina (SPD) e espermina, atuam como moduladores endógenos de diversos canais iônicos, incluindo o subtipo de receptor glutamatérgico N-metil-D-aspartato (NMDAr). A administração sistêmica e intra-cerebral de SPD melhora a memória em diversas tarefas em roedores. Recentemente foi demonstrado que a administração sistêmica de SPD, melhora a persistência e a reconsolidação da memória na tarefa de medo condicionado contextual, em ratos. Entretanto, faltam estudos a fim de elucidar o mecanismo de ação e as estruturas cerebrais envolvidas no efeito das poliaminas nestas fases da memória. Portanto, o objetivo deste estudo foi avaliar o efeito da infusão intra-hipocampal de SPD na persistência da memória e na persistência da reconsolidação da memória, de animais submetidos a tarefa de medo condicionado contextual. Além disso, verificar o envolvimento do NMDAr, da síntese protéica e da proteína cinase dependente de AMPc (PKA), na persistência da memória. Bem como, o envolvimento da expressão do BDNF e da neurogênese na persistência da reconsolidação da memória. Assim, ratos Wistar machos adultos foram submetidos ao treino na tarefa de medo condicionado contextual e, 12 h pós-treino, receberam uma infusão intra-hipocampal de SPD (0,02-2 nmol/sítio), arcaína (0,02-2 nmol/sítio), um antagonista competitivo do sítio de ligação das poliaminas no NMDAr, assim como, do inibidor da síntese proteica, (anisomicina, 2-20 μg/sítio) e do inibidor da PKA (H-89, 0,5-10 pmol/sítio). Um grupo de animais foi eutanasiado, 3 h após a injeção de SPD, para posterior avaliação da expressão da PKA hipocampal. Outro grupo de animais, foi testado 2 ou 7 dias após o treino. Enquanto a infusão intra- hipocampal de SPD (2 nmol/sítio) melhorou a persistência da memória, a infusão intra-hipocampal de arcaína (2 nmol/sítio) e anisomicina (20 μg/sítio) prejudicaram a persistência da memória dos animais testados 7 dias após o treinamento. A arcaína (0,2 nmol/sítio), a anisomicina (2 μg/sítio) e o H-89 (10 pmol/sítio), nas doses que não possuem efeito per se, preveniram a melhora da persistência da memória induzida por SPD (2 nmol/sítio). A SPD (2 nmol/sítio) aumentou a expressão da fosfo-PKA/total-PKA, enquanto o H-89 (10 pmol/sítio) preveniu o aumento da fosfo- PKA/total-PKA induzida por SPD. Além disso, avaliou-se o efeito das poliaminas na persistência da reconsolidação da memória. Para isto, ratos Wistar machos adultos foram treinados na tarefa de medo condicionado contextual, 24 h pós-treino a memória foi reativada, e 0, 6, 12 ou 24 h pós-reativação, receberam uma infusão intra-hipocampal de SPD (0.02-2 nmol/sítio). Um grupo de animais foi eutanasiado, 3 h após a injeção de SPD, e o hipocampo foi removido para posterior avaliação da expressão do BDNF maduro e total. Outro grupo de animais foi testado 2 ou 7 dias após a reativação. A SPD (2 nmol/sítio) infundida 0 h ou 12 h pós-reativação, melhorou a persistência da reconsolidação da memória, somente dos animais testados 7 dias após a reativação. Além disso, a SPD (2 nmol/sítio) infundida 12 h pós-reativação, aumentou a expressão do BDNF maduro, mas não do BDNF total no hipocampo de ratos. Aliado a isso, estudos in vitro demostraram que a SPD aumentou o número de neuritos, a migração celular e os níveis de BDNF em células progenitoras neuronais. Portanto, os resultados do presente estudo sugerem uma modulação positiva das poliaminas no NMDAr hipocampal, da síntese proteica e da PKA, na fase de persistência da memória. Bem como, sugere-se o envolvimento da SPD na persistência da reconsolidação da memória provavelmente através de mecanismos que facilitem o aumento da expressão de BDNF maduro hipocampal e da neurogênese.Conselho Nacional de Pesquisa e Desenvolvimento Científico e Tecnológico - CNPqporUniversidade 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/openAccessPoliaminasPersistência da memóriaPersistência da reconsolidação da memóriaMedo condicionado contextualPKABDNFPolyaminesPersistence of memoryPersistence of reconsolidation of memoryContextual fear conditioningCNPQ::CIENCIAS BIOLOGICAS::BIOQUIMICAInfusão intra-hipocampal de espermidina melhora a persistência da memória e a persistência da reconsolidação da memória em ratosIntra-hippocampal spermidine improves the persistence of memory and the persistence of reconsolidation of memory in ratsinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/doctoralThesisRubin, Maribel Antonellohttp://lattes.cnpq.br/7237734243628134Carpes, Pâmela Billig Mellohttp://lattes.cnpq.br/0450761543923331Bianchin, Marino Muxfeldthttp://lattes.cnpq.br/9451268033505401Oliveira, Sara Marchesan dehttp://lattes.cnpq.br/6574555059806902Rosemberg, Denis Broockhttp://lattes.cnpq.br/7713953979203056http://lattes.cnpq.br/3720944651505539Signor, Cristiane20080000000260017f72a93-232f-40b3-9c14-1b54b978789b80b7ba1f-c870-43ad-b499-f37bba04f2b05928ef8e-96e3-43f4-8865-22a4561fac1b4d75703e-9584-48f9-bb12-c7f0d19d0e89d049731b-07b6-48d8-b4ad-6c096b325f61607e382a-3bee-4345-8f96-b68eed3a31d3reponame:Biblioteca Digital de Teses e Dissertações do UFSMinstname:Universidade Federal de Santa Maria (UFSM)instacron:UFSMCC-LICENSElicense_rdflicense_rdfapplication/rdf+xml; charset=utf-8805http://repositorio.ufsm.br/bitstream/1/18049/2/license_rdf4460e5956bc1d1639be9ae6146a50347MD52LICENSElicense.txtlicense.txttext/plain; charset=utf-81956http://repositorio.ufsm.br/bitstream/1/18049/3/license.txt2f0571ecee68693bd5cd3f17c1e075dfMD53ORIGINALTES_PPGCBBT_2016_SIGNOR_CRISTIANE.pdfTES_PPGCBBT_2016_SIGNOR_CRISTIANE.pdfTese de Doutoradoapplication/pdf4829872http://repositorio.ufsm.br/bitstream/1/18049/1/TES_PPGCBBT_2016_SIGNOR_CRISTIANE.pdf89bd2d4f8f2c9e5606aaf23e827c66a7MD51TEXTTES_PPGCBBT_2016_SIGNOR_CRISTIANE.pdf.txtTES_PPGCBBT_2016_SIGNOR_CRISTIANE.pdf.txtExtracted texttext/plain163003http://repositorio.ufsm.br/bitstream/1/18049/4/TES_PPGCBBT_2016_SIGNOR_CRISTIANE.pdf.txt799bce190c09d90d4744532adeb1da29MD54THUMBNAILTES_PPGCBBT_2016_SIGNOR_CRISTIANE.pdf.jpgTES_PPGCBBT_2016_SIGNOR_CRISTIANE.pdf.jpgIM Thumbnailimage/jpeg4846http://repositorio.ufsm.br/bitstream/1/18049/5/TES_PPGCBBT_2016_SIGNOR_CRISTIANE.pdf.jpgfedc3a25e0cc38531aa61125d07312e9MD551/180492019-08-29 03:02:11.694oai:repositorio.ufsm.br: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 Digital de Teses e Dissertaçõeshttps://repositorio.ufsm.br/ONGhttps://repositorio.ufsm.br/oai/requestatendimento.sib@ufsm.br||tedebc@gmail.comopendoar:2019-08-29T06:02:11Biblioteca Digital de Teses e Dissertações do UFSM - Universidade Federal de Santa Maria (UFSM)false |
dc.title.por.fl_str_mv |
Infusão intra-hipocampal de espermidina melhora a persistência da memória e a persistência da reconsolidação da memória em ratos |
dc.title.alternative.eng.fl_str_mv |
Intra-hippocampal spermidine improves the persistence of memory and the persistence of reconsolidation of memory in rats |
title |
Infusão intra-hipocampal de espermidina melhora a persistência da memória e a persistência da reconsolidação da memória em ratos |
spellingShingle |
Infusão intra-hipocampal de espermidina melhora a persistência da memória e a persistência da reconsolidação da memória em ratos Signor, Cristiane Poliaminas Persistência da memória Persistência da reconsolidação da memória Medo condicionado contextual PKA BDNF Polyamines Persistence of memory Persistence of reconsolidation of memory Contextual fear conditioning CNPQ::CIENCIAS BIOLOGICAS::BIOQUIMICA |
title_short |
Infusão intra-hipocampal de espermidina melhora a persistência da memória e a persistência da reconsolidação da memória em ratos |
title_full |
Infusão intra-hipocampal de espermidina melhora a persistência da memória e a persistência da reconsolidação da memória em ratos |
title_fullStr |
Infusão intra-hipocampal de espermidina melhora a persistência da memória e a persistência da reconsolidação da memória em ratos |
title_full_unstemmed |
Infusão intra-hipocampal de espermidina melhora a persistência da memória e a persistência da reconsolidação da memória em ratos |
title_sort |
Infusão intra-hipocampal de espermidina melhora a persistência da memória e a persistência da reconsolidação da memória em ratos |
author |
Signor, Cristiane |
author_facet |
Signor, Cristiane |
author_role |
author |
dc.contributor.advisor1.fl_str_mv |
Rubin, Maribel Antonello |
dc.contributor.advisor1Lattes.fl_str_mv |
http://lattes.cnpq.br/7237734243628134 |
dc.contributor.referee1.fl_str_mv |
Carpes, Pâmela Billig Mello |
dc.contributor.referee1Lattes.fl_str_mv |
http://lattes.cnpq.br/0450761543923331 |
dc.contributor.referee2.fl_str_mv |
Bianchin, Marino Muxfeldt |
dc.contributor.referee2Lattes.fl_str_mv |
http://lattes.cnpq.br/9451268033505401 |
dc.contributor.referee3.fl_str_mv |
Oliveira, Sara Marchesan de |
dc.contributor.referee3Lattes.fl_str_mv |
http://lattes.cnpq.br/6574555059806902 |
dc.contributor.referee4.fl_str_mv |
Rosemberg, Denis Broock |
dc.contributor.referee4Lattes.fl_str_mv |
http://lattes.cnpq.br/7713953979203056 |
dc.contributor.authorLattes.fl_str_mv |
http://lattes.cnpq.br/3720944651505539 |
dc.contributor.author.fl_str_mv |
Signor, Cristiane |
contributor_str_mv |
Rubin, Maribel Antonello Carpes, Pâmela Billig Mello Bianchin, Marino Muxfeldt Oliveira, Sara Marchesan de Rosemberg, Denis Broock |
dc.subject.por.fl_str_mv |
Poliaminas Persistência da memória Persistência da reconsolidação da memória Medo condicionado contextual PKA BDNF |
topic |
Poliaminas Persistência da memória Persistência da reconsolidação da memória Medo condicionado contextual PKA BDNF Polyamines Persistence of memory Persistence of reconsolidation of memory Contextual fear conditioning CNPQ::CIENCIAS BIOLOGICAS::BIOQUIMICA |
dc.subject.eng.fl_str_mv |
Polyamines Persistence of memory Persistence of reconsolidation of memory Contextual fear conditioning |
dc.subject.cnpq.fl_str_mv |
CNPQ::CIENCIAS BIOLOGICAS::BIOQUIMICA |
description |
The persistence of memory requires a delayed healing process (12-24 h after the acquisition) wherein the synthesis of new proteins and derived neurotrophic factor (BDNF), are essential. The polyamines putrescine, spermidine (SPD) and spermine, they act as endogenous modulators of various ion channels, including the glutamatergic receptor subtype N-methyl-D-aspartate (NMDAr). Systemic administration and intracerebral SPD improves memory in various tasks in rodents. It has recently been demonstrated that systemic administration of SPD improves the persistence and reconsolidation of memory in contextual fear conditioning task in rats. However, there are few studies to elucidate the mechanism of action and the brain structures involved in the effect of polyamines in these stages of memory. Therefore, the aim of this study was to evaluate the effect of intra-hippocampal infusion of SPD in the persistence of memory and the persistence of memory reconsolidation of animals subjected to contextual fear conditioning task. Also, check the involvement of NMDAr, protein synthesis and protein kinase dependent on cAMP (PKA), in the persistence of memory. We also investigated the involvement of BDNF expression and neurogenesis in persistent memory reconsolidation. Thus, adult male Wistar rats were submitted to training in contextual fear conditioning task, and 12 h post-training, received an intra-hippocampal infusion SPD (0.02-2 nmol/site), arcaine (0.02-2 nmol/site), a competitive antagonist of the polyamine NMDAr binding site as well as the protein synthesis inhibitor (anisomycin, 2-20 μg/site) and PKA inhibitor (H- 89 0.5-10 pmol/site). One group of animals was euthanized, 3 h after injection of SPD, for further evaluation of the expression of hippocampal PKA. Another group of animals was tested 2 or 7 days after training. While intra-hippocampal infusion SPD (2 nmol/site) improved the persistence of memory, arcaine (2 nmol/site) and anisomycin (20 μg/site) impaired the persistence of memory of the animals tested 7 days after training. The arcaine (0.2 nmol/ site), the anisomycin (2 μg/site) and H-89 (10 pmol/site), at doses that have no effect per se, prevented the improvement of the persistence of memory induced by SPD (2 nmol/ site). The SPD (2 nmol/site) increased the expression of phospho-PKA/total-PKA, while the H-89 (10 pmol/site) prevented the increase in phospho-PKA/total-PKA-induced SPD. In addition, we evaluated the effect of polyamines in persistent memory reconsolidation. For this, Wistar adult male rats were trained in contextual fear conditioning task, 24 h post- training memory has been reactivated, and 0, 6, 12 or 24 h post-reactivation received an intra-hippocampal infusion SPD (0.02- 2 nmol/ site). One group of animals was euthanized 3 h after injection of SPD and the hippocampus was removed for later evaluation of the expression of total and mature BDNF. Another group of animals was tested 2 or 7 days after the reactivation. The SPD (2 nmol/site) infused 0 h and 12 h post-reactivation, improved the persistence of reconsolidation of memory, only in animals tested 7 days after reactivation. Moreover, the SPD (2 nmol/site) infused 12 h after reactivation increased the expression of mature BDNF, but not the total BDNF in rat hippocampus. In vitro studies demonstrated that the SPD increased the number of neurites, migration cell and levels of BDNF in neural progenitor cells. Therefore, the present results suggest an upregulation of polyamines in hippocampal NMDAr, protein synthesis and PKA in the memory persistence phase. This study also suggests the involvement of the SPD in persistent memory reconsolidation probably through mechanism to facilitate the increase in mature hippocampal BDNF expression and neurogenesis. |
publishDate |
2016 |
dc.date.issued.fl_str_mv |
2016-08-19 |
dc.date.accessioned.fl_str_mv |
2019-08-28T11:03:23Z |
dc.date.available.fl_str_mv |
2019-08-28T11:03:23Z |
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/1/18049 |
url |
http://repositorio.ufsm.br/handle/1/18049 |
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 |
17f72a93-232f-40b3-9c14-1b54b978789b 80b7ba1f-c870-43ad-b499-f37bba04f2b0 5928ef8e-96e3-43f4-8865-22a4561fac1b 4d75703e-9584-48f9-bb12-c7f0d19d0e89 d049731b-07b6-48d8-b4ad-6c096b325f61 607e382a-3bee-4345-8f96-b68eed3a31d3 |
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/1/18049/2/license_rdf http://repositorio.ufsm.br/bitstream/1/18049/3/license.txt http://repositorio.ufsm.br/bitstream/1/18049/1/TES_PPGCBBT_2016_SIGNOR_CRISTIANE.pdf http://repositorio.ufsm.br/bitstream/1/18049/4/TES_PPGCBBT_2016_SIGNOR_CRISTIANE.pdf.txt http://repositorio.ufsm.br/bitstream/1/18049/5/TES_PPGCBBT_2016_SIGNOR_CRISTIANE.pdf.jpg |
bitstream.checksum.fl_str_mv |
4460e5956bc1d1639be9ae6146a50347 2f0571ecee68693bd5cd3f17c1e075df 89bd2d4f8f2c9e5606aaf23e827c66a7 799bce190c09d90d4744532adeb1da29 fedc3a25e0cc38531aa61125d07312e9 |
bitstream.checksumAlgorithm.fl_str_mv |
MD5 MD5 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_ |
1793239996228960256 |