Papel da Na+, K+ - ATPase no modelo de epilepsia do lobo temporal em camundongos
Autor(a) principal: | |
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Data de Publicação: | 2015 |
Tipo de documento: | Tese |
Idioma: | por |
Título da fonte: | Repositório Institucional Manancial UFSM |
Texto Completo: | http://repositorio.ufsm.br/handle/1/3845 |
Resumo: | Epilepsy is a disease that affects about 1-2% of the general population. Considering the high number of patients with epilepsy who are refractory to currently available drugs, it is important to search for new anticonvulsant drugs. For this it is important that reproduces model epilepsy, such as the pilocarpine model, a muscarinic agonist causing limbic seizures and status epilepticus, which after a latency period is characterized by a temporal lobe epilepsy. A potential drug target in the treatment of epilepsy is the Na+,K+-ATPase, which is characterized by being a plasma membrane protein having important role in the maintenance of cellular ionic homeostasis, changes in the Na+,K+-ATPase activity directly affect cell signaling via neurotransmitters and neuronal activity. In this context, a impair the functioning of the Na+,K+-ATPase leads to an increased or decreased neuronal excitability, depending on the degree of inhibition induced neuronal and type affected. Therefore, the present study searched for the role of Na+,K+-ATPase and the specific antibody that enhances the activity of Na+,K+-ATPase (DRRSAb) in the pilocarpine model in C57BL/6 mice challenged with pentylenetetrazol (PTZ). It was seen that the activity of Na+,K+-ATPase was decreased in hippocampus of epileptic mice, 60 days after status epilepticus (SE). Furthermore, the Michelis-Menten constant for different ATP concentrations increased in the SE. Reduced activity of Na+,K+-ATPase appears to involve the nitration of α subunit, but no changes in the expression or its phosphorylation state at Ser943 was found. Interestingly, activation of Na+,K+-ATPase intrahippocampal injection with a specific antibody (DRRSAb) produced against a regulatory site of the α subunit, decreases susceptibility to myoclonic seizures induced by PTZ in epileptic animals. On the other hand, the administration of DRRSAb in the hippocampus of naive animals facilitated the onset of seizures induced by PTZ. Quantitative analysis of hippocampal EEG recordings revealed that DRRSAb increased the percentage of total power contributed by delta frequency band (0-3 Hz) to large irregular amplitude pattern of hippocampal EEG. On the other hand, no DRRSAb-induced changes were found regarding the theta functional state. Therefore, activation of Na+,K+-ATPase activity as a novel approach in seizure disorders, may become a potential target for epilepsy. |
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2015-05-262015-05-262015-03-16FUNCK, Vinícius Rafael. Role of Na+ K+ - ATPase in a model temporal lobe epilepsy in mice. 2015. 95 f. Tese (Doutorado em Farmácia) - Universidade Federal de Santa Maria, Santa Maria, 2015.http://repositorio.ufsm.br/handle/1/3845Epilepsy is a disease that affects about 1-2% of the general population. Considering the high number of patients with epilepsy who are refractory to currently available drugs, it is important to search for new anticonvulsant drugs. For this it is important that reproduces model epilepsy, such as the pilocarpine model, a muscarinic agonist causing limbic seizures and status epilepticus, which after a latency period is characterized by a temporal lobe epilepsy. A potential drug target in the treatment of epilepsy is the Na+,K+-ATPase, which is characterized by being a plasma membrane protein having important role in the maintenance of cellular ionic homeostasis, changes in the Na+,K+-ATPase activity directly affect cell signaling via neurotransmitters and neuronal activity. In this context, a impair the functioning of the Na+,K+-ATPase leads to an increased or decreased neuronal excitability, depending on the degree of inhibition induced neuronal and type affected. Therefore, the present study searched for the role of Na+,K+-ATPase and the specific antibody that enhances the activity of Na+,K+-ATPase (DRRSAb) in the pilocarpine model in C57BL/6 mice challenged with pentylenetetrazol (PTZ). It was seen that the activity of Na+,K+-ATPase was decreased in hippocampus of epileptic mice, 60 days after status epilepticus (SE). Furthermore, the Michelis-Menten constant for different ATP concentrations increased in the SE. Reduced activity of Na+,K+-ATPase appears to involve the nitration of α subunit, but no changes in the expression or its phosphorylation state at Ser943 was found. Interestingly, activation of Na+,K+-ATPase intrahippocampal injection with a specific antibody (DRRSAb) produced against a regulatory site of the α subunit, decreases susceptibility to myoclonic seizures induced by PTZ in epileptic animals. On the other hand, the administration of DRRSAb in the hippocampus of naive animals facilitated the onset of seizures induced by PTZ. Quantitative analysis of hippocampal EEG recordings revealed that DRRSAb increased the percentage of total power contributed by delta frequency band (0-3 Hz) to large irregular amplitude pattern of hippocampal EEG. On the other hand, no DRRSAb-induced changes were found regarding the theta functional state. Therefore, activation of Na+,K+-ATPase activity as a novel approach in seizure disorders, may become a potential target for epilepsy.A epilepsia é uma doença que atinge cerca de 1 % da população em geral. Embora vários tratamentos farmacológicos sejam utilizados, um elevado número de pacientes com epilepsia são refratários às drogas disponíveis atualmente o que torna importante à busca por novas drogas anticonvulsivantes. Para isso, é necessário um modelo que reproduza a epilepsia, como é o caso do modelo da pilocarpina, um agonista muscarínico que causa convulsões límbicas e status epilepticus (SE), que após crises recorrentes se caracteriza por uma epilepsia do lobo temporal. Um possível alvo farmacológico na terapia da epilepsia é a enzima Na+, K+-ATPase, que se caracteriza por ser uma proteína de membrana plasmática que tem um papel importante na manutenção da homeostase iônica celular cuja mudança na atividade da Na+, K+-ATPase afeta diretamente a sinalização celular via neurotransmissores e a atividade neuronal. Neste contexto, um prejuízo ao funcionamento da Na+, K+-ATPase ocasiona aumento ou diminuição da excitabilidade neuronal, dependendo do grau de inibição induzido e do tipo neuronal afetado. Portanto, o presente estudo, procurou o papel da Na+, K+-ATPase e de um anticorpo específico que aumenta a atividade da Na+, K+-ATPase (DRRSAb), no modelo da pilocarpina em camundongos C57BL/6 e sobre a susceptibilidade ao pentilenotetrazol (PTZ). Foi constatado que a atividade da Na+, K+-ATPase está diminuída no hipocampo de camundongos 60 dias após o SE. Além disso, a constante de Michelis-Menten para as diferentes concentrações de ATP aumentou no grupo pós-SE. A redução da atividade da Na+,K+-ATPase parece envolver a nitração da subunidade α, mas nenhuma alteração na expressão ou no estado de fosforilação na Ser943 foi encontrada. Interessantemente, a ativação da Na+, K+-ATPase, com uma injeção intrahipocampal do anticorpo DRRSAb produzido contra um local regulador da subunidade α, diminui a susceptibilidade para crises mioclônicas induzida por PTZ nos animais epilépticos. Por outro lado, a administração de DRRSAb no hipocampo de animais normais facilitou o aparecimento de convulsões induzidas por PTZ. A análise quantitativa do registro eletroencefalográfico (EEG) no hipocampo, revelou que o DRRSAb aumentou a porcentagem de poder total na frequência da banda delta (0-3 Hz), quando analisado padrão de atividade irregular de grande amplitude (LIA). Por outro lado, não houve alterações induzidas pelo DRRSAb sobre o estado funcional do ritmo teta. Portanto, a ativação Na+, K+-ATPase, como uma nova abordagem em distúrbios convulsivos, pode tornar-se um alvo farmacológico em potencial na epilepsia.Coordenação de Aperfeiçoamento de Pessoal de Nível Superiorapplication/pdfporUniversidade Federal de Santa MariaPrograma de Pós-Graduação em FarmacologiaUFSMBRFarmacologiaEpilepsia do lobo temporalNa+, K+-ATPasePilocarpinaTemporal lobe epilepsyPilocarpineCNPQ::CIENCIAS BIOLOGICAS::FARMACOLOGIAPapel da Na+, K+ - ATPase no modelo de epilepsia do lobo temporal em camundongosRole of Na+ K+ - ATPase in a model temporal lobe epilepsy in miceinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/doctoralThesisOliveira, Mauro Schneiderhttp://lattes.cnpq.br/7132934163734175Jesse, Cristiano Ricardohttp://lattes.cnpq.br/0215511072119335Burger, Marilise Escobarhttp://lattes.cnpq.br/9128090974948413Gonçalves, Jamile Fabbrinhttp://lattes.cnpq.br/3517679241506587Mello, Carlos Fernando dehttp://lattes.cnpq.br/3913887223894236http://lattes.cnpq.br/6401593292343704Funck, Vinícius Rafael20100000000040030030030030030030085c7bcbb-76c9-41fa-9c05-5216c865f0b4c482d506-cf0f-4933-8644-8ac20263c8de288da5c4-855a-4f9e-a357-c33d01032a48a609a359-a0e0-4c67-b9c2-5c029e49529cab81ec88-9851-4ead-b8b9-6dce887dc3ef34c50b38-c4f8-4e1c-8fe0-f403608ad63dinfo:eu-repo/semantics/openAccessreponame:Repositório Institucional Manancial UFSMinstname:Universidade Federal de Santa Maria (UFSM)instacron:UFSMORIGINALFUNCK, VINICIUS RAFAEL.pdfapplication/pdf4631536http://repositorio.ufsm.br/bitstream/1/3845/1/FUNCK%2c%20VINICIUS%20RAFAEL.pdffb41a3903f5e9ae0371699cb3a78ca51MD51TEXTFUNCK, VINICIUS RAFAEL.pdf.txtFUNCK, VINICIUS RAFAEL.pdf.txtExtracted texttext/plain136416http://repositorio.ufsm.br/bitstream/1/3845/2/FUNCK%2c%20VINICIUS%20RAFAEL.pdf.txt29a69510a5123206e2c19cbf098da853MD52THUMBNAILFUNCK, VINICIUS RAFAEL.pdf.jpgFUNCK, VINICIUS RAFAEL.pdf.jpgIM Thumbnailimage/jpeg4883http://repositorio.ufsm.br/bitstream/1/3845/3/FUNCK%2c%20VINICIUS%20RAFAEL.pdf.jpg6935c36ee76891d05119dd2c453b8d02MD531/38452022-09-06 10:43:06.288oai:repositorio.ufsm.br:1/3845Repositório Institucionalhttp://repositorio.ufsm.br/PUBhttp://repositorio.ufsm.br/oai/requestouvidoria@ufsm.bropendoar:39132022-09-06T13:43:06Repositório Institucional Manancial UFSM - Universidade Federal de Santa Maria (UFSM)false |
dc.title.por.fl_str_mv |
Papel da Na+, K+ - ATPase no modelo de epilepsia do lobo temporal em camundongos |
dc.title.alternative.eng.fl_str_mv |
Role of Na+ K+ - ATPase in a model temporal lobe epilepsy in mice |
title |
Papel da Na+, K+ - ATPase no modelo de epilepsia do lobo temporal em camundongos |
spellingShingle |
Papel da Na+, K+ - ATPase no modelo de epilepsia do lobo temporal em camundongos Funck, Vinícius Rafael Epilepsia do lobo temporal Na+, K+-ATPase Pilocarpina Temporal lobe epilepsy Pilocarpine CNPQ::CIENCIAS BIOLOGICAS::FARMACOLOGIA |
title_short |
Papel da Na+, K+ - ATPase no modelo de epilepsia do lobo temporal em camundongos |
title_full |
Papel da Na+, K+ - ATPase no modelo de epilepsia do lobo temporal em camundongos |
title_fullStr |
Papel da Na+, K+ - ATPase no modelo de epilepsia do lobo temporal em camundongos |
title_full_unstemmed |
Papel da Na+, K+ - ATPase no modelo de epilepsia do lobo temporal em camundongos |
title_sort |
Papel da Na+, K+ - ATPase no modelo de epilepsia do lobo temporal em camundongos |
author |
Funck, Vinícius Rafael |
author_facet |
Funck, Vinícius Rafael |
author_role |
author |
dc.contributor.advisor1.fl_str_mv |
Oliveira, Mauro Schneider |
dc.contributor.advisor1Lattes.fl_str_mv |
http://lattes.cnpq.br/7132934163734175 |
dc.contributor.referee1.fl_str_mv |
Jesse, Cristiano Ricardo |
dc.contributor.referee1Lattes.fl_str_mv |
http://lattes.cnpq.br/0215511072119335 |
dc.contributor.referee2.fl_str_mv |
Burger, Marilise Escobar |
dc.contributor.referee2Lattes.fl_str_mv |
http://lattes.cnpq.br/9128090974948413 |
dc.contributor.referee3.fl_str_mv |
Gonçalves, Jamile Fabbrin |
dc.contributor.referee3Lattes.fl_str_mv |
http://lattes.cnpq.br/3517679241506587 |
dc.contributor.referee4.fl_str_mv |
Mello, Carlos Fernando de |
dc.contributor.referee4Lattes.fl_str_mv |
http://lattes.cnpq.br/3913887223894236 |
dc.contributor.authorLattes.fl_str_mv |
http://lattes.cnpq.br/6401593292343704 |
dc.contributor.author.fl_str_mv |
Funck, Vinícius Rafael |
contributor_str_mv |
Oliveira, Mauro Schneider Jesse, Cristiano Ricardo Burger, Marilise Escobar Gonçalves, Jamile Fabbrin Mello, Carlos Fernando de |
dc.subject.por.fl_str_mv |
Epilepsia do lobo temporal Na+, K+-ATPase Pilocarpina |
topic |
Epilepsia do lobo temporal Na+, K+-ATPase Pilocarpina Temporal lobe epilepsy Pilocarpine CNPQ::CIENCIAS BIOLOGICAS::FARMACOLOGIA |
dc.subject.eng.fl_str_mv |
Temporal lobe epilepsy Pilocarpine |
dc.subject.cnpq.fl_str_mv |
CNPQ::CIENCIAS BIOLOGICAS::FARMACOLOGIA |
description |
Epilepsy is a disease that affects about 1-2% of the general population. Considering the high number of patients with epilepsy who are refractory to currently available drugs, it is important to search for new anticonvulsant drugs. For this it is important that reproduces model epilepsy, such as the pilocarpine model, a muscarinic agonist causing limbic seizures and status epilepticus, which after a latency period is characterized by a temporal lobe epilepsy. A potential drug target in the treatment of epilepsy is the Na+,K+-ATPase, which is characterized by being a plasma membrane protein having important role in the maintenance of cellular ionic homeostasis, changes in the Na+,K+-ATPase activity directly affect cell signaling via neurotransmitters and neuronal activity. In this context, a impair the functioning of the Na+,K+-ATPase leads to an increased or decreased neuronal excitability, depending on the degree of inhibition induced neuronal and type affected. Therefore, the present study searched for the role of Na+,K+-ATPase and the specific antibody that enhances the activity of Na+,K+-ATPase (DRRSAb) in the pilocarpine model in C57BL/6 mice challenged with pentylenetetrazol (PTZ). It was seen that the activity of Na+,K+-ATPase was decreased in hippocampus of epileptic mice, 60 days after status epilepticus (SE). Furthermore, the Michelis-Menten constant for different ATP concentrations increased in the SE. Reduced activity of Na+,K+-ATPase appears to involve the nitration of α subunit, but no changes in the expression or its phosphorylation state at Ser943 was found. Interestingly, activation of Na+,K+-ATPase intrahippocampal injection with a specific antibody (DRRSAb) produced against a regulatory site of the α subunit, decreases susceptibility to myoclonic seizures induced by PTZ in epileptic animals. On the other hand, the administration of DRRSAb in the hippocampus of naive animals facilitated the onset of seizures induced by PTZ. Quantitative analysis of hippocampal EEG recordings revealed that DRRSAb increased the percentage of total power contributed by delta frequency band (0-3 Hz) to large irregular amplitude pattern of hippocampal EEG. On the other hand, no DRRSAb-induced changes were found regarding the theta functional state. Therefore, activation of Na+,K+-ATPase activity as a novel approach in seizure disorders, may become a potential target for epilepsy. |
publishDate |
2015 |
dc.date.accessioned.fl_str_mv |
2015-05-26 |
dc.date.available.fl_str_mv |
2015-05-26 |
dc.date.issued.fl_str_mv |
2015-03-16 |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/doctoralThesis |
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doctoralThesis |
status_str |
publishedVersion |
dc.identifier.citation.fl_str_mv |
FUNCK, Vinícius Rafael. Role of Na+ K+ - ATPase in a model temporal lobe epilepsy in mice. 2015. 95 f. Tese (Doutorado em Farmácia) - Universidade Federal de Santa Maria, Santa Maria, 2015. |
dc.identifier.uri.fl_str_mv |
http://repositorio.ufsm.br/handle/1/3845 |
identifier_str_mv |
FUNCK, Vinícius Rafael. Role of Na+ K+ - ATPase in a model temporal lobe epilepsy in mice. 2015. 95 f. Tese (Doutorado em Farmácia) - Universidade Federal de Santa Maria, Santa Maria, 2015. |
url |
http://repositorio.ufsm.br/handle/1/3845 |
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por |
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UFSM |
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Farmacologia |
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Universidade Federal de Santa Maria |
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