Constitutive hippocampal cholesterol loss underlies poor cognition in old rodents

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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 the precise mechanisms underlying LTP and LTD dampening in the old remain unclear. We previously showed that agi...

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Autores principales:	Martín, Mauricio Gerardo, Ahmed, Tariq, Korovaichuk, Alejandra, Venero, César, Menchón, Silvia Adriana, Salas, Isabel, Munck, Sebastian, Herreras, Oscar, Balschun, Detlef, Dotti, Carlos Gerardo
Formato:	article
Lenguaje:	Inglés
Publicado:	2021
Materias:	Aging Cholesterol Learning LTD PI3K Neuroscience Long-term depression
Acceso en línea:	http://hdl.handle.net/11086/20817 https://doi.org/10.15252/emmm.201303711
Aporte de:	Repositorio Digital Universitario (UNC) de Universidad Nacional de Córdoba

id	I10-R14111086-20817
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institution	Universidad Nacional de Córdoba
institution_str	I-10
repository_str	R-141
collection	Repositorio Digital Universitario (UNC)
language	Inglés
topic	Aging Cholesterol Learning LTD PI3K Neuroscience Long-term depression
spellingShingle	Aging Cholesterol Learning LTD PI3K Neuroscience Long-term depression Martín, Mauricio Gerardo Ahmed, Tariq Korovaichuk, Alejandra Venero, César Menchón, Silvia Adriana Salas, Isabel Munck, Sebastian Herreras, Oscar Balschun, Detlef Dotti, Carlos Gerardo Constitutive hippocampal cholesterol loss underlies poor cognition in old rodents
topic_facet	Aging Cholesterol Learning LTD PI3K Neuroscience Long-term depression
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 the precise mechanisms underlying LTP and LTD dampening in the old remain unclear. We previously showed that aging is accompanied by the loss of cholesterol from the hippocampus, which leads to PI3K/Akt phosphorylation. Given that Akt de-phosphorylation is required for glutamate receptor internalization and LTD, we hypothesized that the decrease in cholesterol in neuronal membranes 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 molecular responses induced by LTD, such as impaired AMPA receptor internalization and its reduced lateral diffusion. Electrophysiology recordings in brain slices of old mice and in anesthetized elderly rats demonstrate that the reduced hippocampal LTD associated with age can be rescued by cholesterol perfusion. Accordingly, cholesterol replenishment in aging animals improves hippocampal-dependent learning and memory in the water maze test.
format	article
author	Martín, Mauricio Gerardo Ahmed, Tariq Korovaichuk, Alejandra Venero, César Menchón, Silvia Adriana Salas, Isabel Munck, Sebastian Herreras, Oscar Balschun, Detlef Dotti, Carlos 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 Gerardo
author_sort	Martín, Mauricio Gerardo
title	Constitutive hippocampal cholesterol loss underlies poor cognition in old rodents
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
publishDate	2021
url	http://hdl.handle.net/11086/20817 https://doi.org/10.15252/emmm.201303711
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Constitutive hippocampal cholesterol loss underlies poor cognition in old rodents

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