Reduced expression of hippocampal GluN2A-NMDAR increases seizure susceptibility and causes deficits in contextual memory

Autores
Acutain, Maria Florencia; Griebler Luft, Jordana; Vázquez, Cecilia Alejandra; Popik, Bruno; Cercato, Magalí Cecilia; Epstein, Alberto; Salvetti, Anna; Jerusalinsky, Diana Alicia; de Oliveira Alvares, Lucas; Baez, Maria Veronica
Año de publicación
2021
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
N-methyl-D-aspartate receptors are heterotetramers composed of two GluN1 obligatory subunits and two regulatory subunits. In cognitive-related brain structures, GluN2A and GluN2B are the most abundant regulatory subunits, and their expression is subjected to tight regulation. During development, GluN2B expression is characteristic of immature synapses, whereas GluN2A is present in mature ones. This change in expression induces a shift in GluN2A/GluN2B ratio known as developmental switch. Moreover, modifications in this relationship have been associated with learning and memory, as well as different pathologies. In this work, we used a specific shRNA to induce a reduction in GluN2A expression after the developmental switch, both in vitro in primary cultured hippocampal neurons and in vivo in adult male Wistar rats. After in vitro characterization, we performed a cognitive profile and evaluated seizure susceptibility in vivo. Our in vitro results showed that the decrease in the expression of GluN2A changes GluN2A/GluN2B ratio without altering the expression of other regulatory subunits. Moreover, rats expressing the anti-GluN2A shRNA in vivo displayed an impaired contextual fear-conditioning memory. In addition, these animals showed increased seizure susceptibility, in terms of both time and intensity, which led us to conclude that deregulation in GluN2A expression at the hippocampus is associated with seizure susceptibility and learning–memory mechanisms.
Fil: Acutain, Maria Florencia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; Argentina
Fil: Griebler Luft, Jordana. Universidade Federal do Rio Grande do Sul; Brasil
Fil: Vázquez, Cecilia Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; Argentina
Fil: Popik, Bruno. Universidade Federal do Rio Grande do Sul; Brasil
Fil: Cercato, Magalí Cecilia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; Argentina
Fil: Epstein, Alberto. Universite Lyon 2; Francia
Fil: Salvetti, Anna. Inserm; Francia
Fil: Jerusalinsky, Diana Alicia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; Argentina
Fil: de Oliveira Alvares, Lucas. Universidade Federal do Rio Grande do Sul; Brasil
Fil: Baez, Maria Veronica. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; Argentina
Materia
GLUN2A SUBUNIT
GLUN2A/GLUN2B
HIPPOCAMPUS
LONG-TERM MEMORY
MRNA SILENCING
NMDA RECEPTORS
SEIZURE INDUCTION
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/168626
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/168626
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Reduced expression of hippocampal GluN2A-NMDAR increases seizure susceptibility and causes deficits in contextual memoryAcutain, Maria FlorenciaGriebler Luft, JordanaVázquez, Cecilia AlejandraPopik, BrunoCercato, Magalí CeciliaEpstein, AlbertoSalvetti, AnnaJerusalinsky, Diana Aliciade Oliveira Alvares, LucasBaez, Maria VeronicaGLUN2A SUBUNITGLUN2A/GLUN2BHIPPOCAMPUSLONG-TERM MEMORYMRNA SILENCINGNMDA RECEPTORSSEIZURE INDUCTIONhttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3N-methyl-D-aspartate receptors are heterotetramers composed of two GluN1 obligatory subunits and two regulatory subunits. In cognitive-related brain structures, GluN2A and GluN2B are the most abundant regulatory subunits, and their expression is subjected to tight regulation. During development, GluN2B expression is characteristic of immature synapses, whereas GluN2A is present in mature ones. This change in expression induces a shift in GluN2A/GluN2B ratio known as developmental switch. Moreover, modifications in this relationship have been associated with learning and memory, as well as different pathologies. In this work, we used a specific shRNA to induce a reduction in GluN2A expression after the developmental switch, both in vitro in primary cultured hippocampal neurons and in vivo in adult male Wistar rats. After in vitro characterization, we performed a cognitive profile and evaluated seizure susceptibility in vivo. Our in vitro results showed that the decrease in the expression of GluN2A changes GluN2A/GluN2B ratio without altering the expression of other regulatory subunits. Moreover, rats expressing the anti-GluN2A shRNA in vivo displayed an impaired contextual fear-conditioning memory. In addition, these animals showed increased seizure susceptibility, in terms of both time and intensity, which led us to conclude that deregulation in GluN2A expression at the hippocampus is associated with seizure susceptibility and learning–memory mechanisms.Fil: Acutain, Maria Florencia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; ArgentinaFil: Griebler Luft, Jordana. Universidade Federal do Rio Grande do Sul; BrasilFil: Vázquez, Cecilia Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; ArgentinaFil: Popik, Bruno. Universidade Federal do Rio Grande do Sul; BrasilFil: Cercato, Magalí Cecilia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; ArgentinaFil: Epstein, Alberto. Universite Lyon 2; FranciaFil: Salvetti, Anna. Inserm; FranciaFil: Jerusalinsky, Diana Alicia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; ArgentinaFil: de Oliveira Alvares, Lucas. Universidade Federal do Rio Grande do Sul; BrasilFil: Baez, Maria Veronica. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; ArgentinaFrontiers Media2021-04info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/168626Acutain, Maria Florencia; Griebler Luft, Jordana; Vázquez, Cecilia Alejandra; Popik, Bruno; Cercato, Magalí Cecilia; et al.; Reduced expression of hippocampal GluN2A-NMDAR increases seizure susceptibility and causes deficits in contextual memory; Frontiers Media; Frontiers in Neuroscience; 15; 4-2021; 1-151662-453XCONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://www.frontiersin.org/articles/10.3389/fnins.2021.644100/abstractinfo:eu-repo/semantics/altIdentifier/doi/10.3389/fnins.2021.644100info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-10T13:09:02Zoai:ri.conicet.gov.ar:11336/168626instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-10 13:09:03.034CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Reduced expression of hippocampal GluN2A-NMDAR increases seizure susceptibility and causes deficits in contextual memory
title Reduced expression of hippocampal GluN2A-NMDAR increases seizure susceptibility and causes deficits in contextual memory
spellingShingle Reduced expression of hippocampal GluN2A-NMDAR increases seizure susceptibility and causes deficits in contextual memory
Acutain, Maria Florencia
GLUN2A SUBUNIT
GLUN2A/GLUN2B
HIPPOCAMPUS
LONG-TERM MEMORY
MRNA SILENCING
NMDA RECEPTORS
SEIZURE INDUCTION
title_short Reduced expression of hippocampal GluN2A-NMDAR increases seizure susceptibility and causes deficits in contextual memory
title_full Reduced expression of hippocampal GluN2A-NMDAR increases seizure susceptibility and causes deficits in contextual memory
title_fullStr Reduced expression of hippocampal GluN2A-NMDAR increases seizure susceptibility and causes deficits in contextual memory
title_full_unstemmed Reduced expression of hippocampal GluN2A-NMDAR increases seizure susceptibility and causes deficits in contextual memory
title_sort Reduced expression of hippocampal GluN2A-NMDAR increases seizure susceptibility and causes deficits in contextual memory
dc.creator.none.fl_str_mv Acutain, Maria Florencia
Griebler Luft, Jordana
Vázquez, Cecilia Alejandra
Popik, Bruno
Cercato, Magalí Cecilia
Epstein, Alberto
Salvetti, Anna
Jerusalinsky, Diana Alicia
de Oliveira Alvares, Lucas
Baez, Maria Veronica
author Acutain, Maria Florencia
author_facet Acutain, Maria Florencia
Griebler Luft, Jordana
Vázquez, Cecilia Alejandra
Popik, Bruno
Cercato, Magalí Cecilia
Epstein, Alberto
Salvetti, Anna
Jerusalinsky, Diana Alicia
de Oliveira Alvares, Lucas
Baez, Maria Veronica
author_role author
author2 Griebler Luft, Jordana
Vázquez, Cecilia Alejandra
Popik, Bruno
Cercato, Magalí Cecilia
Epstein, Alberto
Salvetti, Anna
Jerusalinsky, Diana Alicia
de Oliveira Alvares, Lucas
Baez, Maria Veronica
author2_role author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv GLUN2A SUBUNIT
GLUN2A/GLUN2B
HIPPOCAMPUS
LONG-TERM MEMORY
MRNA SILENCING
NMDA RECEPTORS
SEIZURE INDUCTION
topic GLUN2A SUBUNIT
GLUN2A/GLUN2B
HIPPOCAMPUS
LONG-TERM MEMORY
MRNA SILENCING
NMDA RECEPTORS
SEIZURE INDUCTION
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv N-methyl-D-aspartate receptors are heterotetramers composed of two GluN1 obligatory subunits and two regulatory subunits. In cognitive-related brain structures, GluN2A and GluN2B are the most abundant regulatory subunits, and their expression is subjected to tight regulation. During development, GluN2B expression is characteristic of immature synapses, whereas GluN2A is present in mature ones. This change in expression induces a shift in GluN2A/GluN2B ratio known as developmental switch. Moreover, modifications in this relationship have been associated with learning and memory, as well as different pathologies. In this work, we used a specific shRNA to induce a reduction in GluN2A expression after the developmental switch, both in vitro in primary cultured hippocampal neurons and in vivo in adult male Wistar rats. After in vitro characterization, we performed a cognitive profile and evaluated seizure susceptibility in vivo. Our in vitro results showed that the decrease in the expression of GluN2A changes GluN2A/GluN2B ratio without altering the expression of other regulatory subunits. Moreover, rats expressing the anti-GluN2A shRNA in vivo displayed an impaired contextual fear-conditioning memory. In addition, these animals showed increased seizure susceptibility, in terms of both time and intensity, which led us to conclude that deregulation in GluN2A expression at the hippocampus is associated with seizure susceptibility and learning–memory mechanisms.
Fil: Acutain, Maria Florencia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; Argentina
Fil: Griebler Luft, Jordana. Universidade Federal do Rio Grande do Sul; Brasil
Fil: Vázquez, Cecilia Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; Argentina
Fil: Popik, Bruno. Universidade Federal do Rio Grande do Sul; Brasil
Fil: Cercato, Magalí Cecilia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; Argentina
Fil: Epstein, Alberto. Universite Lyon 2; Francia
Fil: Salvetti, Anna. Inserm; Francia
Fil: Jerusalinsky, Diana Alicia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; Argentina
Fil: de Oliveira Alvares, Lucas. Universidade Federal do Rio Grande do Sul; Brasil
Fil: Baez, Maria Veronica. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; Argentina
description N-methyl-D-aspartate receptors are heterotetramers composed of two GluN1 obligatory subunits and two regulatory subunits. In cognitive-related brain structures, GluN2A and GluN2B are the most abundant regulatory subunits, and their expression is subjected to tight regulation. During development, GluN2B expression is characteristic of immature synapses, whereas GluN2A is present in mature ones. This change in expression induces a shift in GluN2A/GluN2B ratio known as developmental switch. Moreover, modifications in this relationship have been associated with learning and memory, as well as different pathologies. In this work, we used a specific shRNA to induce a reduction in GluN2A expression after the developmental switch, both in vitro in primary cultured hippocampal neurons and in vivo in adult male Wistar rats. After in vitro characterization, we performed a cognitive profile and evaluated seizure susceptibility in vivo. Our in vitro results showed that the decrease in the expression of GluN2A changes GluN2A/GluN2B ratio without altering the expression of other regulatory subunits. Moreover, rats expressing the anti-GluN2A shRNA in vivo displayed an impaired contextual fear-conditioning memory. In addition, these animals showed increased seizure susceptibility, in terms of both time and intensity, which led us to conclude that deregulation in GluN2A expression at the hippocampus is associated with seizure susceptibility and learning–memory mechanisms.
publishDate 2021
dc.date.none.fl_str_mv 2021-04
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/168626
Acutain, Maria Florencia; Griebler Luft, Jordana; Vázquez, Cecilia Alejandra; Popik, Bruno; Cercato, Magalí Cecilia; et al.; Reduced expression of hippocampal GluN2A-NMDAR increases seizure susceptibility and causes deficits in contextual memory; Frontiers Media; Frontiers in Neuroscience; 15; 4-2021; 1-15
1662-453X
CONICET Digital
CONICET
url http://hdl.handle.net/11336/168626
identifier_str_mv Acutain, Maria Florencia; Griebler Luft, Jordana; Vázquez, Cecilia Alejandra; Popik, Bruno; Cercato, Magalí Cecilia; et al.; Reduced expression of hippocampal GluN2A-NMDAR increases seizure susceptibility and causes deficits in contextual memory; Frontiers Media; Frontiers in Neuroscience; 15; 4-2021; 1-15
1662-453X
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/https://www.frontiersin.org/articles/10.3389/fnins.2021.644100/abstract
info:eu-repo/semantics/altIdentifier/doi/10.3389/fnins.2021.644100
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
application/pdf
dc.publisher.none.fl_str_mv Frontiers Media
publisher.none.fl_str_mv Frontiers Media
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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score 12.993085

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