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
- Institución
- Consejo Nacional de Investigaciones Científicas y Técnicas
- OAI Identificador
- oai:ri.conicet.gov.ar:11336/31842
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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 Técnicas2025-09-29T10:43:23Zoai: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:34982025-09-29 10:43:23.667CONICET 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 |
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1844614469008752640 |
score |
13.070432 |