A Neuroligin-1 mutation associated with Alzheimer's disease produces memory and age-dependent impairments in hippocampal plasticity

Alzheimer's disease (AD) is characterized by memory impairments and age-dependent synapse loss. Experimental and clinical studies have shown decreased expression of the glutamatergic protein Neuroligin-1 (Nlgn1) in AD. However, the consequences of a sustained reduction of Nlgn1 are unknown. Her...

ver descrição completa

Detalhes bibliográficos
Autores: Arias-Aragón, Francisco, Tristán Clavijo, E., Martínez-Gallego, Irene, Robles Lanuza, Estefanía, Coatl-Cuaya, Heriberto, Martín-Cuevas, Celia, Sánchez-Hidalgo, Ana C., Rodríguez-Moreno, Antonio, Martínez Mir, Amalia, Scholl, Francisco G.
Formato: artículo
Estado:Versión publicada
Fecha de publicación:2023
País:España
Recursos:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/335625
Acesso em linha:http://hdl.handle.net/10261/335625
https://api.elsevier.com/content/abstract/scopus_id/85159865330
Access Level:acceso abierto
Palavra-chave:Molecular neuroscience
Behavioral neuroscience
Cellular neuroscience
id ES_0de3dbf877aa6b14ede8f73f9cdfd8e9
oai_identifier_str oai:digital.csic.es:10261/335625
network_acronym_str ES
network_name_str España
repository_id_str
spelling A Neuroligin-1 mutation associated with Alzheimer's disease produces memory and age-dependent impairments in hippocampal plasticityArias-Aragón, FranciscoTristán Clavijo, E.Martínez-Gallego, IreneRobles Lanuza, EstefaníaCoatl-Cuaya, HeribertoMartín-Cuevas, CeliaSánchez-Hidalgo, Ana C.Rodríguez-Moreno, AntonioMartínez Mir, AmaliaScholl, Francisco G.Molecular neuroscienceBehavioral neuroscienceCellular neuroscienceAlzheimer's disease (AD) is characterized by memory impairments and age-dependent synapse loss. Experimental and clinical studies have shown decreased expression of the glutamatergic protein Neuroligin-1 (Nlgn1) in AD. However, the consequences of a sustained reduction of Nlgn1 are unknown. Here, we generated a knockin mouse that reproduces the NLGN1 Thr271fs mutation, identified in heterozygosis in a familial case of AD. We found that Nlgn1 Thr271fs mutation abolishes Nlgn1 expression in mouse brain. Importantly, heterozygous Nlgn1 Thr271fs mice showed delay-dependent amnesia for recognition memory. Electrophysiological recordings uncovered age-dependent impairments in basal synaptic transmission and long-term potentiation (LTP) in CA1 hippocampal neurons of heterozygous Nlgn1 Thr271fs mice. In contrast, homozygous Nlgn1 Thr271fs mice showed impaired fear-conditioning memory and normal basal synaptic transmission, suggesting unshared mechanisms for a partial or total loss of Nlgn1. These data suggest that decreased Nlgn1 may contribute to the synaptic and memory deficits in AD.This work was funded by grants from Ministerio de Ciencia, Innovación y Universidades (RTI2018-101886-B-100) and Junta de Andalucía (PROYEXCEL_00573) to FGS and AM-M, AEI/FEDER (PID2019107677GBI00) and Juan de Andalucía/FEDER (P20_00881) to A.R.-M. and co-funded by ERDF. We thank Sonia Carrasco-Poley for support with NeuN quantification. FA-A was the recipient of a fellowship from Ministerio de Economía, Industria y Competitividad (BES-2016-076579). IM-G was supported by Formación de Profesorado Universitario predoctoral fellowship from Ministerio de Universidades (FPU 17/04283). ER-L was a fellow from V Plan Propio de Investigación (Universidad de Sevilla). CM-C was the recipient of a Garantía Juvenil contract from Universidad de Sevilla. ACS-H received a fellowship from Junta de Andalucía (P11-CVI-7599).Peer reviewedElsevierMinisterio de Ciencia, Innovación y Universidades (España)Junta de AndalucíaMinisterio de Economía y Competitividad (España)Agencia Estatal de Investigación (España)European CommissionUniversidad de SevillaConsejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]202320232023info:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_6501Publisher's versioninfo:eu-repo/semantics/publishedVersionapplication/pdfhttp://hdl.handle.net/10261/335625https://api.elsevier.com/content/abstract/scopus_id/85159865330reponame:DIGITAL.CSIC. Repositorio Institucional del CSICinstname:Consejo Superior de Investigaciones Científicas (CSIC)Inglés#PLACEHOLDER_PARENT_METADATA_VALUE##PLACEHOLDER_PARENT_METADATA_VALUE##PLACEHOLDER_PARENT_METADATA_VALUE#info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020/RTI2018-101886-B-I00info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020/PID2019-107677GB-I00info:eu-repo/grantAgreement/AEI//BES-2016-076579Arias-Aragón, Francisco; Tristán Clavijo, E.; Martínez-Gallego, Irene; Robles Lanuza, Estefanía; Coatl-Cuaya, Heriberto; Martín-Cuevas, Celia; Sánchez-Hidalgo, Ana C.; Rodríguez-Moreno, Antonio; Martínez Mir, Amalia; Scholl, Francisco G.; 2023; Supplemental information. A Neuroligin-1 mutation associated with Alzheimer’s disease produces memory and age-dependent impairments in hippocampal plasticity [Dataset]; Elsevier; https://doi.org/10.1016/j.isci.2023.106868https://doi.org/10.1016/j.isci.2023.106868Síinfo:eu-repo/semantics/openAccessoai:digital.csic.es:10261/3356252026-05-22T06:33:51Z
dc.title.none.fl_str_mv A Neuroligin-1 mutation associated with Alzheimer's disease produces memory and age-dependent impairments in hippocampal plasticity
title A Neuroligin-1 mutation associated with Alzheimer's disease produces memory and age-dependent impairments in hippocampal plasticity
spellingShingle A Neuroligin-1 mutation associated with Alzheimer's disease produces memory and age-dependent impairments in hippocampal plasticity
Arias-Aragón, Francisco
Molecular neuroscience
Behavioral neuroscience
Cellular neuroscience
title_short A Neuroligin-1 mutation associated with Alzheimer's disease produces memory and age-dependent impairments in hippocampal plasticity
title_full A Neuroligin-1 mutation associated with Alzheimer's disease produces memory and age-dependent impairments in hippocampal plasticity
title_fullStr A Neuroligin-1 mutation associated with Alzheimer's disease produces memory and age-dependent impairments in hippocampal plasticity
title_full_unstemmed A Neuroligin-1 mutation associated with Alzheimer's disease produces memory and age-dependent impairments in hippocampal plasticity
title_sort A Neuroligin-1 mutation associated with Alzheimer's disease produces memory and age-dependent impairments in hippocampal plasticity
dc.creator.none.fl_str_mv Arias-Aragón, Francisco
Tristán Clavijo, E.
Martínez-Gallego, Irene
Robles Lanuza, Estefanía
Coatl-Cuaya, Heriberto
Martín-Cuevas, Celia
Sánchez-Hidalgo, Ana C.
Rodríguez-Moreno, Antonio
Martínez Mir, Amalia
Scholl, Francisco G.
author Arias-Aragón, Francisco
author_facet Arias-Aragón, Francisco
Tristán Clavijo, E.
Martínez-Gallego, Irene
Robles Lanuza, Estefanía
Coatl-Cuaya, Heriberto
Martín-Cuevas, Celia
Sánchez-Hidalgo, Ana C.
Rodríguez-Moreno, Antonio
Martínez Mir, Amalia
Scholl, Francisco G.
author_role author
author2 Tristán Clavijo, E.
Martínez-Gallego, Irene
Robles Lanuza, Estefanía
Coatl-Cuaya, Heriberto
Martín-Cuevas, Celia
Sánchez-Hidalgo, Ana C.
Rodríguez-Moreno, Antonio
Martínez Mir, Amalia
Scholl, Francisco G.
author2_role author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Ministerio de Ciencia, Innovación y Universidades (España)
Junta de Andalucía
Ministerio de Economía y Competitividad (España)
Agencia Estatal de Investigación (España)
European Commission
Universidad de Sevilla
Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]
dc.subject.none.fl_str_mv Molecular neuroscience
Behavioral neuroscience
Cellular neuroscience
topic Molecular neuroscience
Behavioral neuroscience
Cellular neuroscience
description Alzheimer's disease (AD) is characterized by memory impairments and age-dependent synapse loss. Experimental and clinical studies have shown decreased expression of the glutamatergic protein Neuroligin-1 (Nlgn1) in AD. However, the consequences of a sustained reduction of Nlgn1 are unknown. Here, we generated a knockin mouse that reproduces the NLGN1 Thr271fs mutation, identified in heterozygosis in a familial case of AD. We found that Nlgn1 Thr271fs mutation abolishes Nlgn1 expression in mouse brain. Importantly, heterozygous Nlgn1 Thr271fs mice showed delay-dependent amnesia for recognition memory. Electrophysiological recordings uncovered age-dependent impairments in basal synaptic transmission and long-term potentiation (LTP) in CA1 hippocampal neurons of heterozygous Nlgn1 Thr271fs mice. In contrast, homozygous Nlgn1 Thr271fs mice showed impaired fear-conditioning memory and normal basal synaptic transmission, suggesting unshared mechanisms for a partial or total loss of Nlgn1. These data suggest that decreased Nlgn1 may contribute to the synaptic and memory deficits in AD.
publishDate 2023
dc.date.none.fl_str_mv 2023
2023
2023
dc.type.none.fl_str_mv info:eu-repo/semantics/article
http://purl.org/coar/resource_type/c_6501
Publisher's version
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10261/335625
https://api.elsevier.com/content/abstract/scopus_id/85159865330
url http://hdl.handle.net/10261/335625
https://api.elsevier.com/content/abstract/scopus_id/85159865330
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv #PLACEHOLDER_PARENT_METADATA_VALUE#
#PLACEHOLDER_PARENT_METADATA_VALUE#
#PLACEHOLDER_PARENT_METADATA_VALUE#
info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020/RTI2018-101886-B-I00
info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020/PID2019-107677GB-I00
info:eu-repo/grantAgreement/AEI//BES-2016-076579
Arias-Aragón, Francisco; Tristán Clavijo, E.; Martínez-Gallego, Irene; Robles Lanuza, Estefanía; Coatl-Cuaya, Heriberto; Martín-Cuevas, Celia; Sánchez-Hidalgo, Ana C.; Rodríguez-Moreno, Antonio; Martínez Mir, Amalia; Scholl, Francisco G.; 2023; Supplemental information. A Neuroligin-1 mutation associated with Alzheimer’s disease produces memory and age-dependent impairments in hippocampal plasticity [Dataset]; Elsevier; https://doi.org/10.1016/j.isci.2023.106868
https://doi.org/10.1016/j.isci.2023.106868
Sí
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Elsevier
publisher.none.fl_str_mv Elsevier
dc.source.none.fl_str_mv reponame:DIGITAL.CSIC. Repositorio Institucional del CSIC
instname:Consejo Superior de Investigaciones Científicas (CSIC)
instname_str Consejo Superior de Investigaciones Científicas (CSIC)
reponame_str DIGITAL.CSIC. Repositorio Institucional del CSIC
collection DIGITAL.CSIC. Repositorio Institucional del CSIC
repository.name.fl_str_mv
repository.mail.fl_str_mv
_version_ 1869403365009522688
score 15,81155

Registos relacionados