Activation of D1/D5 Dopamine Receptors Protects Neurons from Synapse Dysfunction Induced by Amyloid-beta Oligomers
Autor(a) principal: | |
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Data de Publicação: | 2011 |
Outros Autores: | , , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Institucional da UNIFESP |
Texto Completo: | http://repositorio.unifesp.br/handle/11600/33461 http://dx.doi.org/10.1074/jbc.M110.177790 |
Resumo: | Soluble oligomers of the amyloid-beta peptide (A beta Os) accumulate in the brains of Alzheimer disease (AD) patients and are implicated in synapse failure and early memory loss in AD. A beta Os have been shown to impact synapse function by inhibiting long term potentiation, facilitating the induction of long term depression and inducing internalization of both AMPA and NMDA glutamate receptors, critical players in plasticity mechanisms. Because activation of dopamine D1/D5 receptors plays important roles in memory circuits by increasing the insertion of AMPA and NMDA receptors at synapses, we hypothesized that selective activation of D1/D5 receptors could protect synapses from the deleterious action of A beta Os. We show that SKF81297, a selective D1/D5 receptor agonist, prevented the reduction in surface levels of AMPA and NMDA receptors induced by A beta Os in hippocampal neurons in culture. Protection by SKF81297 was abrogated by the specific D1/D5 antagonist, SCH23390. Levels of AMPA receptor subunit GluR1 phosphorylated at Ser(845), which regulates AMPA receptor association with the plasma membrane, were reduced in a calcineurin-dependent manner in the presence of A beta Os, and treatment with SKF81297 prevented this reduction. Establishing the functional relevance of these findings, SKF81297 blocked the impairment of long term potentiation induced by A beta Os in hippocampal slices. Results suggest that D1/D5 receptors may be relevant targets for development of novel pharmacological approaches to prevent synapse failure in AD. |
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Juergensen, SofiaAntônio, Leandro Leite [UNIFESP]Mussi, Gabriela E. A.Brito-Moreira, JordanoBomfim, Theresa R.De Felice, Fernanda G.Garrido-Sanabria, Emilio R.Cavalheiro, Esper Abrão [UNIFESP]Ferreira, Sergio T.Universidade Federal do Rio de Janeiro (UFRJ)Universidade Federal de São Paulo (UNIFESP)Univ Texas Brownsville2016-01-24T14:06:11Z2016-01-24T14:06:11Z2011-02-04Journal of Biological Chemistry. Bethesda: Amer Soc Biochemistry Molecular Biology Inc, v. 286, n. 5, p. 3270-3276, 2011.0021-9258http://repositorio.unifesp.br/handle/11600/33461http://dx.doi.org/10.1074/jbc.M110.17779010.1074/jbc.M110.177790WOS:000286653200012Soluble oligomers of the amyloid-beta peptide (A beta Os) accumulate in the brains of Alzheimer disease (AD) patients and are implicated in synapse failure and early memory loss in AD. A beta Os have been shown to impact synapse function by inhibiting long term potentiation, facilitating the induction of long term depression and inducing internalization of both AMPA and NMDA glutamate receptors, critical players in plasticity mechanisms. Because activation of dopamine D1/D5 receptors plays important roles in memory circuits by increasing the insertion of AMPA and NMDA receptors at synapses, we hypothesized that selective activation of D1/D5 receptors could protect synapses from the deleterious action of A beta Os. We show that SKF81297, a selective D1/D5 receptor agonist, prevented the reduction in surface levels of AMPA and NMDA receptors induced by A beta Os in hippocampal neurons in culture. Protection by SKF81297 was abrogated by the specific D1/D5 antagonist, SCH23390. Levels of AMPA receptor subunit GluR1 phosphorylated at Ser(845), which regulates AMPA receptor association with the plasma membrane, were reduced in a calcineurin-dependent manner in the presence of A beta Os, and treatment with SKF81297 prevented this reduction. Establishing the functional relevance of these findings, SKF81297 blocked the impairment of long term potentiation induced by A beta Os in hippocampal slices. Results suggest that D1/D5 receptors may be relevant targets for development of novel pharmacological approaches to prevent synapse failure in AD.National Institutes of HealthConselho Nacional de Desenvolvimento Cientifico TecnologicoInstituto Nacional de Neurociencia TranslacionalCoordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Fundação de Amparo à Pesquisa do Estado do Rio de Janeiro (FAPERJ)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Human Frontier Science ProgramUniv Fed Rio de Janeiro, Inst Med Biochem, BR-1944590 Rio de Janeiro, BrazilUniversidade Federal de São Paulo, Dept Expt Neurol, BR-04023900 São Paulo, BrazilUniv Texas Brownsville, Ctr Biomed Studies, Dept Biol Sci, Brownsville, TX 78520 USAUniversidade Federal de São Paulo, Dept Expt Neurol, BR-04023900 São Paulo, BrazilNational Institutes of Health: 5SC1NS063950-04National Institutes of Health: 3SC1NS063950-03S1Web of Science3270-3276engAmer Soc Biochemistry Molecular Biology IncJournal of Biological ChemistryActivation of D1/D5 Dopamine Receptors Protects Neurons from Synapse Dysfunction Induced by Amyloid-beta Oligomersinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleinfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da UNIFESPinstname:Universidade Federal de São Paulo (UNIFESP)instacron:UNIFESP11600/334612022-09-27 11:18:57.908metadata only accessoai:repositorio.unifesp.br:11600/33461Repositório InstitucionalPUBhttp://www.repositorio.unifesp.br/oai/requestopendoar:34652022-09-27T14:18:57Repositório Institucional da UNIFESP - Universidade Federal de São Paulo (UNIFESP)false |
dc.title.en.fl_str_mv |
Activation of D1/D5 Dopamine Receptors Protects Neurons from Synapse Dysfunction Induced by Amyloid-beta Oligomers |
title |
Activation of D1/D5 Dopamine Receptors Protects Neurons from Synapse Dysfunction Induced by Amyloid-beta Oligomers |
spellingShingle |
Activation of D1/D5 Dopamine Receptors Protects Neurons from Synapse Dysfunction Induced by Amyloid-beta Oligomers Juergensen, Sofia |
title_short |
Activation of D1/D5 Dopamine Receptors Protects Neurons from Synapse Dysfunction Induced by Amyloid-beta Oligomers |
title_full |
Activation of D1/D5 Dopamine Receptors Protects Neurons from Synapse Dysfunction Induced by Amyloid-beta Oligomers |
title_fullStr |
Activation of D1/D5 Dopamine Receptors Protects Neurons from Synapse Dysfunction Induced by Amyloid-beta Oligomers |
title_full_unstemmed |
Activation of D1/D5 Dopamine Receptors Protects Neurons from Synapse Dysfunction Induced by Amyloid-beta Oligomers |
title_sort |
Activation of D1/D5 Dopamine Receptors Protects Neurons from Synapse Dysfunction Induced by Amyloid-beta Oligomers |
author |
Juergensen, Sofia |
author_facet |
Juergensen, Sofia Antônio, Leandro Leite [UNIFESP] Mussi, Gabriela E. A. Brito-Moreira, Jordano Bomfim, Theresa R. De Felice, Fernanda G. Garrido-Sanabria, Emilio R. Cavalheiro, Esper Abrão [UNIFESP] Ferreira, Sergio T. |
author_role |
author |
author2 |
Antônio, Leandro Leite [UNIFESP] Mussi, Gabriela E. A. Brito-Moreira, Jordano Bomfim, Theresa R. De Felice, Fernanda G. Garrido-Sanabria, Emilio R. Cavalheiro, Esper Abrão [UNIFESP] Ferreira, Sergio T. |
author2_role |
author author author author author author author author |
dc.contributor.institution.none.fl_str_mv |
Universidade Federal do Rio de Janeiro (UFRJ) Universidade Federal de São Paulo (UNIFESP) Univ Texas Brownsville |
dc.contributor.author.fl_str_mv |
Juergensen, Sofia Antônio, Leandro Leite [UNIFESP] Mussi, Gabriela E. A. Brito-Moreira, Jordano Bomfim, Theresa R. De Felice, Fernanda G. Garrido-Sanabria, Emilio R. Cavalheiro, Esper Abrão [UNIFESP] Ferreira, Sergio T. |
description |
Soluble oligomers of the amyloid-beta peptide (A beta Os) accumulate in the brains of Alzheimer disease (AD) patients and are implicated in synapse failure and early memory loss in AD. A beta Os have been shown to impact synapse function by inhibiting long term potentiation, facilitating the induction of long term depression and inducing internalization of both AMPA and NMDA glutamate receptors, critical players in plasticity mechanisms. Because activation of dopamine D1/D5 receptors plays important roles in memory circuits by increasing the insertion of AMPA and NMDA receptors at synapses, we hypothesized that selective activation of D1/D5 receptors could protect synapses from the deleterious action of A beta Os. We show that SKF81297, a selective D1/D5 receptor agonist, prevented the reduction in surface levels of AMPA and NMDA receptors induced by A beta Os in hippocampal neurons in culture. Protection by SKF81297 was abrogated by the specific D1/D5 antagonist, SCH23390. Levels of AMPA receptor subunit GluR1 phosphorylated at Ser(845), which regulates AMPA receptor association with the plasma membrane, were reduced in a calcineurin-dependent manner in the presence of A beta Os, and treatment with SKF81297 prevented this reduction. Establishing the functional relevance of these findings, SKF81297 blocked the impairment of long term potentiation induced by A beta Os in hippocampal slices. Results suggest that D1/D5 receptors may be relevant targets for development of novel pharmacological approaches to prevent synapse failure in AD. |
publishDate |
2011 |
dc.date.issued.fl_str_mv |
2011-02-04 |
dc.date.accessioned.fl_str_mv |
2016-01-24T14:06:11Z |
dc.date.available.fl_str_mv |
2016-01-24T14:06:11Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.citation.fl_str_mv |
Journal of Biological Chemistry. Bethesda: Amer Soc Biochemistry Molecular Biology Inc, v. 286, n. 5, p. 3270-3276, 2011. |
dc.identifier.uri.fl_str_mv |
http://repositorio.unifesp.br/handle/11600/33461 http://dx.doi.org/10.1074/jbc.M110.177790 |
dc.identifier.issn.none.fl_str_mv |
0021-9258 |
dc.identifier.doi.none.fl_str_mv |
10.1074/jbc.M110.177790 |
dc.identifier.wos.none.fl_str_mv |
WOS:000286653200012 |
identifier_str_mv |
Journal of Biological Chemistry. Bethesda: Amer Soc Biochemistry Molecular Biology Inc, v. 286, n. 5, p. 3270-3276, 2011. 0021-9258 10.1074/jbc.M110.177790 WOS:000286653200012 |
url |
http://repositorio.unifesp.br/handle/11600/33461 http://dx.doi.org/10.1074/jbc.M110.177790 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.ispartof.none.fl_str_mv |
Journal of Biological Chemistry |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
3270-3276 |
dc.publisher.none.fl_str_mv |
Amer Soc Biochemistry Molecular Biology Inc |
publisher.none.fl_str_mv |
Amer Soc Biochemistry Molecular Biology Inc |
dc.source.none.fl_str_mv |
reponame:Repositório Institucional da UNIFESP instname:Universidade Federal de São Paulo (UNIFESP) instacron:UNIFESP |
instname_str |
Universidade Federal de São Paulo (UNIFESP) |
instacron_str |
UNIFESP |
institution |
UNIFESP |
reponame_str |
Repositório Institucional da UNIFESP |
collection |
Repositório Institucional da UNIFESP |
repository.name.fl_str_mv |
Repositório Institucional da UNIFESP - Universidade Federal de São Paulo (UNIFESP) |
repository.mail.fl_str_mv |
|
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1802764170509156352 |