Constitutive hippocampal cholesterol loss underlies poor cognition in old rodents

Autores
Martín, Mauricio Gerardo; Ahmed, Tariq; Korovaichuk, Alejandra; Venero, César; Menchón, Silvia Adriana; Salas, Isabel; Munck, Sebastian; Herreras, Oscar; Balschun, Detlef; Dotti, Carlos G.
Año de publicación
2014
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Cognitive decline is one of the many characteristics of aging.Reduced long-term potentiation (LTP) and long-term depression(LTD) are thought to be responsible for this decline, although theprecise mechanisms underlying LTP and LTD dampening in the oldremain unclear. We previously showed that aging is accompaniedby the loss of cholesterol from the hippocampus, which leads toPI3K/Akt phosphorylation. Given that Akt de-phosphorylation isrequired for glutamate receptor internalization and LTD, wehypothesized that the decrease in cholesterol in neuronalmembranes may contribute to the deficits in LTD typical of aging.Here, we show that cholesterol loss triggers p-Akt accumulation,which in turn perturbs the normal cellular and molecularresponses induced by LTD, such as impaired AMPA receptor inter-nalization and its reduced lateral diffusion. Electrophysiologyrecordings in brain slices of old mice and in anesthetized elderlyrats demonstrate that the reduced hippocampal LTD associatedwith age can be rescued by cholesterol perfusion. Accordingly,cholesterol replenishment in aging animals improves hippocampal-dependent learning and memory in the water maze test.
Fil: Martín, Mauricio Gerardo. Centro Biología Molecular “Severo Ochoa”. Madrid; España. University of Leuven. Leuven; Bélgica. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Ahmed, Tariq. University of Leuven. Leuven; Bélgica
Fil: Korovaichuk, Alejandra. Instituto Cajal. Madrid; España
Fil: Venero, César. Universidad Nacional de Educacion a Distancia; España
Fil: Menchón, Silvia Adriana. University of Leuven. Leuven; Bélgica. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Física Enrique Gaviola. Universidad Nacional de Córdoba. Instituto de Física Enrique Gaviola; Argentina
Fil: Salas, Isabel. Centro Biología Molecular “Severo Ochoa”. Madrid; España
Fil: Munck, Sebastian. University of Leuven. Leuven; Bélgica
Fil: Herreras, Oscar. Instituto Cajal. Madrid; España
Fil: Balschun, Detlef. University of Leuven. Leuven; Bélgica
Fil: Dotti, Carlos G.. Centro Biología Molecular “Severo Ochoa”. Madrid; España. University of Leuven. Leuven; Bélgica
Materia
Ageing
Cholesterol
Neuroscience
Metabolism
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:11336/31842
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/31842
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Constitutive hippocampal cholesterol loss underlies poor cognition in old rodentsMartín, Mauricio GerardoAhmed, TariqKorovaichuk, AlejandraVenero, CésarMenchón, Silvia AdrianaSalas, IsabelMunck, SebastianHerreras, OscarBalschun, DetlefDotti, Carlos G.AgeingCholesterolNeuroscienceMetabolismhttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Cognitive decline is one of the many characteristics of aging.Reduced long-term potentiation (LTP) and long-term depression(LTD) are thought to be responsible for this decline, although theprecise mechanisms underlying LTP and LTD dampening in the oldremain unclear. We previously showed that aging is accompaniedby the loss of cholesterol from the hippocampus, which leads toPI3K/Akt phosphorylation. Given that Akt de-phosphorylation isrequired for glutamate receptor internalization and LTD, wehypothesized that the decrease in cholesterol in neuronalmembranes may contribute to the deficits in LTD typical of aging.Here, we show that cholesterol loss triggers p-Akt accumulation,which in turn perturbs the normal cellular and molecularresponses induced by LTD, such as impaired AMPA receptor inter-nalization and its reduced lateral diffusion. Electrophysiologyrecordings in brain slices of old mice and in anesthetized elderlyrats demonstrate that the reduced hippocampal LTD associatedwith age can be rescued by cholesterol perfusion. Accordingly,cholesterol replenishment in aging animals improves hippocampal-dependent learning and memory in the water maze test.Fil: Martín, Mauricio Gerardo. Centro Biología Molecular “Severo Ochoa”. Madrid; España. University of Leuven. Leuven; Bélgica. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Ahmed, Tariq. University of Leuven. Leuven; BélgicaFil: Korovaichuk, Alejandra. Instituto Cajal. Madrid; EspañaFil: Venero, César. Universidad Nacional de Educacion a Distancia; EspañaFil: Menchón, Silvia Adriana. University of Leuven. Leuven; Bélgica. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Física Enrique Gaviola. Universidad Nacional de Córdoba. Instituto de Física Enrique Gaviola; ArgentinaFil: Salas, Isabel. Centro Biología Molecular “Severo Ochoa”. Madrid; EspañaFil: Munck, Sebastian. University of Leuven. Leuven; BélgicaFil: Herreras, Oscar. Instituto Cajal. Madrid; EspañaFil: Balschun, Detlef. University of Leuven. Leuven; BélgicaFil: Dotti, Carlos G.. Centro Biología Molecular “Severo Ochoa”. Madrid; España. University of Leuven. Leuven; BélgicaWiley Blackwell Publishing, Inc2014-04info: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/11336/31842Dotti, Carlos G.; Balschun, Detlef; Herreras, Oscar; Munck, Sebastian; Salas, Isabel; Menchón, Silvia Adriana; et al.; Constitutive hippocampal cholesterol loss underlies poor cognition in old rodents; Wiley Blackwell Publishing, Inc; Embo Molecular Medicine; 6; 7; 4-2014; 902-9171757-46761757-4684CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.15252/emmm.201303711info:eu-repo/semantics/altIdentifier/url/http://embomolmed.embopress.org/content/6/7/902info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-10-15T15:41:33Zoai:ri.conicet.gov.ar:11336/31842instacron: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:34982025-10-15 15:41:34.074CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Constitutive hippocampal cholesterol loss underlies poor cognition in old rodents
title Constitutive hippocampal cholesterol loss underlies poor cognition in old rodents
spellingShingle Constitutive hippocampal cholesterol loss underlies poor cognition in old rodents
Martín, Mauricio Gerardo
Ageing
Cholesterol
Neuroscience
Metabolism
title_short Constitutive hippocampal cholesterol loss underlies poor cognition in old rodents
title_full Constitutive hippocampal cholesterol loss underlies poor cognition in old rodents
title_fullStr Constitutive hippocampal cholesterol loss underlies poor cognition in old rodents
title_full_unstemmed Constitutive hippocampal cholesterol loss underlies poor cognition in old rodents
title_sort Constitutive hippocampal cholesterol loss underlies poor cognition in old rodents
dc.creator.none.fl_str_mv Martín, Mauricio Gerardo
Ahmed, Tariq
Korovaichuk, Alejandra
Venero, César
Menchón, Silvia Adriana
Salas, Isabel
Munck, Sebastian
Herreras, Oscar
Balschun, Detlef
Dotti, Carlos G.
author Martín, Mauricio Gerardo
author_facet Martín, Mauricio Gerardo
Ahmed, Tariq
Korovaichuk, Alejandra
Venero, César
Menchón, Silvia Adriana
Salas, Isabel
Munck, Sebastian
Herreras, Oscar
Balschun, Detlef
Dotti, Carlos G.
author_role author
author2 Ahmed, Tariq
Korovaichuk, Alejandra
Venero, César
Menchón, Silvia Adriana
Salas, Isabel
Munck, Sebastian
Herreras, Oscar
Balschun, Detlef
Dotti, Carlos G.
author2_role author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Ageing
Cholesterol
Neuroscience
Metabolism
topic Ageing
Cholesterol
Neuroscience
Metabolism
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Cognitive decline is one of the many characteristics of aging.Reduced long-term potentiation (LTP) and long-term depression(LTD) are thought to be responsible for this decline, although theprecise mechanisms underlying LTP and LTD dampening in the oldremain unclear. We previously showed that aging is accompaniedby the loss of cholesterol from the hippocampus, which leads toPI3K/Akt phosphorylation. Given that Akt de-phosphorylation isrequired for glutamate receptor internalization and LTD, wehypothesized that the decrease in cholesterol in neuronalmembranes may contribute to the deficits in LTD typical of aging.Here, we show that cholesterol loss triggers p-Akt accumulation,which in turn perturbs the normal cellular and molecularresponses induced by LTD, such as impaired AMPA receptor inter-nalization and its reduced lateral diffusion. Electrophysiologyrecordings in brain slices of old mice and in anesthetized elderlyrats demonstrate that the reduced hippocampal LTD associatedwith age can be rescued by cholesterol perfusion. Accordingly,cholesterol replenishment in aging animals improves hippocampal-dependent learning and memory in the water maze test.
Fil: Martín, Mauricio Gerardo. Centro Biología Molecular “Severo Ochoa”. Madrid; España. University of Leuven. Leuven; Bélgica. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Ahmed, Tariq. University of Leuven. Leuven; Bélgica
Fil: Korovaichuk, Alejandra. Instituto Cajal. Madrid; España
Fil: Venero, César. Universidad Nacional de Educacion a Distancia; España
Fil: Menchón, Silvia Adriana. University of Leuven. Leuven; Bélgica. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Física Enrique Gaviola. Universidad Nacional de Córdoba. Instituto de Física Enrique Gaviola; Argentina
Fil: Salas, Isabel. Centro Biología Molecular “Severo Ochoa”. Madrid; España
Fil: Munck, Sebastian. University of Leuven. Leuven; Bélgica
Fil: Herreras, Oscar. Instituto Cajal. Madrid; España
Fil: Balschun, Detlef. University of Leuven. Leuven; Bélgica
Fil: Dotti, Carlos G.. Centro Biología Molecular “Severo Ochoa”. Madrid; España. University of Leuven. Leuven; Bélgica
description Cognitive decline is one of the many characteristics of aging.Reduced long-term potentiation (LTP) and long-term depression(LTD) are thought to be responsible for this decline, although theprecise mechanisms underlying LTP and LTD dampening in the oldremain unclear. We previously showed that aging is accompaniedby the loss of cholesterol from the hippocampus, which leads toPI3K/Akt phosphorylation. Given that Akt de-phosphorylation isrequired for glutamate receptor internalization and LTD, wehypothesized that the decrease in cholesterol in neuronalmembranes may contribute to the deficits in LTD typical of aging.Here, we show that cholesterol loss triggers p-Akt accumulation,which in turn perturbs the normal cellular and molecularresponses induced by LTD, such as impaired AMPA receptor inter-nalization and its reduced lateral diffusion. Electrophysiologyrecordings in brain slices of old mice and in anesthetized elderlyrats demonstrate that the reduced hippocampal LTD associatedwith age can be rescued by cholesterol perfusion. Accordingly,cholesterol replenishment in aging animals improves hippocampal-dependent learning and memory in the water maze test.
publishDate 2014
dc.date.none.fl_str_mv 2014-04
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/11336/31842
Dotti, Carlos G.; Balschun, Detlef; Herreras, Oscar; Munck, Sebastian; Salas, Isabel; Menchón, Silvia Adriana; et al.; Constitutive hippocampal cholesterol loss underlies poor cognition in old rodents; Wiley Blackwell Publishing, Inc; Embo Molecular Medicine; 6; 7; 4-2014; 902-917
1757-4676
1757-4684
CONICET Digital
CONICET
url http://hdl.handle.net/11336/31842
identifier_str_mv Dotti, Carlos G.; Balschun, Detlef; Herreras, Oscar; Munck, Sebastian; Salas, Isabel; Menchón, Silvia Adriana; et al.; Constitutive hippocampal cholesterol loss underlies poor cognition in old rodents; Wiley Blackwell Publishing, Inc; Embo Molecular Medicine; 6; 7; 4-2014; 902-917
1757-4676
1757-4684
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.15252/emmm.201303711
info:eu-repo/semantics/altIdentifier/url/http://embomolmed.embopress.org/content/6/7/902
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 Wiley Blackwell Publishing, Inc
publisher.none.fl_str_mv Wiley Blackwell Publishing, Inc
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
_version_ 1846083526302105600
score 13.22299

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