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Age-Dependent Shift of AMPA Receptors From Synapses to Intracellular Compartments in Alzheimer’s Disease: Immunocytochemical Analysis of the CA1 Hippocampal Region in APP/PS1 Transgenic Mouse Model

Synapse loss occurs early in Alzheimer’s disease (AD) patients and animal models. Alterations at synaptic level are a major morphological correlate of the memory deficits and related symptoms of AD. Given the predominant roles of synaptic AMPA receptors (AMPARs) in excitatory synaptic transmission i...

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Autores principales: Martín-Belmonte, Alejandro, Aguado, Carolina, Alfaro-Ruíz, Rocío, Itakura, Makoto, Moreno-Martínez, Ana Esther, de la Ossa, Luis, Molnár, Elek, Fukazawa, Yugo, Luján, Rafael
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7572859/
https://www.ncbi.nlm.nih.gov/pubmed/33132900
http://dx.doi.org/10.3389/fnagi.2020.577996
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author Martín-Belmonte, Alejandro
Aguado, Carolina
Alfaro-Ruíz, Rocío
Itakura, Makoto
Moreno-Martínez, Ana Esther
de la Ossa, Luis
Molnár, Elek
Fukazawa, Yugo
Luján, Rafael
author_facet Martín-Belmonte, Alejandro
Aguado, Carolina
Alfaro-Ruíz, Rocío
Itakura, Makoto
Moreno-Martínez, Ana Esther
de la Ossa, Luis
Molnár, Elek
Fukazawa, Yugo
Luján, Rafael
author_sort Martín-Belmonte, Alejandro
collection PubMed
description Synapse loss occurs early in Alzheimer’s disease (AD) patients and animal models. Alterations at synaptic level are a major morphological correlate of the memory deficits and related symptoms of AD. Given the predominant roles of synaptic AMPA receptors (AMPARs) in excitatory synaptic transmission in the brain, changes in their dynamic regulation are also implicated in the pathophysiology of AD. Here, we used immunolocalization techniques to analyze the expression and subcellular distribution of AMPARs in the hippocampal region of APP/PS1 mouse model of AD. Immunoblots and histoblots revealed that the total amount of AMPARs and their regional expression pattern in the hippocampus was similar in APP/PS1 mice and in age-matched wild type mice. At the ultrastructural level, two synapse populations were examined using SDS-digested freeze-fracture replica labeling in the stratum radiatum in mice: (i) on spines of CA1 pyramidal cells; and (ii) on randomly found dendritic shafts of CA1 interneurons. While 1- and 6-months-old APP/PS1 mice exhibited no change, we observed a significant reduction at 12 months in AMPAR density at synapses in both pyramidal cells and interneurons, compared to wild-type. This reduction of AMPARs in dendritic spines was accompanied by a significant increase in AMPAR subunit proteins identified in intracellular compartments. Our data demonstrate an age-dependent reduction of synaptic AMPARs in APP/PS1 mice, which may contribute to impaired learning and memory at later stages of AD.
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spelling pubmed-75728592020-10-30 Age-Dependent Shift of AMPA Receptors From Synapses to Intracellular Compartments in Alzheimer’s Disease: Immunocytochemical Analysis of the CA1 Hippocampal Region in APP/PS1 Transgenic Mouse Model Martín-Belmonte, Alejandro Aguado, Carolina Alfaro-Ruíz, Rocío Itakura, Makoto Moreno-Martínez, Ana Esther de la Ossa, Luis Molnár, Elek Fukazawa, Yugo Luján, Rafael Front Aging Neurosci Neuroscience Synapse loss occurs early in Alzheimer’s disease (AD) patients and animal models. Alterations at synaptic level are a major morphological correlate of the memory deficits and related symptoms of AD. Given the predominant roles of synaptic AMPA receptors (AMPARs) in excitatory synaptic transmission in the brain, changes in their dynamic regulation are also implicated in the pathophysiology of AD. Here, we used immunolocalization techniques to analyze the expression and subcellular distribution of AMPARs in the hippocampal region of APP/PS1 mouse model of AD. Immunoblots and histoblots revealed that the total amount of AMPARs and their regional expression pattern in the hippocampus was similar in APP/PS1 mice and in age-matched wild type mice. At the ultrastructural level, two synapse populations were examined using SDS-digested freeze-fracture replica labeling in the stratum radiatum in mice: (i) on spines of CA1 pyramidal cells; and (ii) on randomly found dendritic shafts of CA1 interneurons. While 1- and 6-months-old APP/PS1 mice exhibited no change, we observed a significant reduction at 12 months in AMPAR density at synapses in both pyramidal cells and interneurons, compared to wild-type. This reduction of AMPARs in dendritic spines was accompanied by a significant increase in AMPAR subunit proteins identified in intracellular compartments. Our data demonstrate an age-dependent reduction of synaptic AMPARs in APP/PS1 mice, which may contribute to impaired learning and memory at later stages of AD. Frontiers Media S.A. 2020-10-06 /pmc/articles/PMC7572859/ /pubmed/33132900 http://dx.doi.org/10.3389/fnagi.2020.577996 Text en Copyright © 2020 Martín-Belmonte, Aguado, Alfaro-Ruíz, Itakura, Moreno-Martínez, de la Ossa, Molnár, Fukazawa and Luján. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Neuroscience
Martín-Belmonte, Alejandro
Aguado, Carolina
Alfaro-Ruíz, Rocío
Itakura, Makoto
Moreno-Martínez, Ana Esther
de la Ossa, Luis
Molnár, Elek
Fukazawa, Yugo
Luján, Rafael
Age-Dependent Shift of AMPA Receptors From Synapses to Intracellular Compartments in Alzheimer’s Disease: Immunocytochemical Analysis of the CA1 Hippocampal Region in APP/PS1 Transgenic Mouse Model
title Age-Dependent Shift of AMPA Receptors From Synapses to Intracellular Compartments in Alzheimer’s Disease: Immunocytochemical Analysis of the CA1 Hippocampal Region in APP/PS1 Transgenic Mouse Model
title_full Age-Dependent Shift of AMPA Receptors From Synapses to Intracellular Compartments in Alzheimer’s Disease: Immunocytochemical Analysis of the CA1 Hippocampal Region in APP/PS1 Transgenic Mouse Model
title_fullStr Age-Dependent Shift of AMPA Receptors From Synapses to Intracellular Compartments in Alzheimer’s Disease: Immunocytochemical Analysis of the CA1 Hippocampal Region in APP/PS1 Transgenic Mouse Model
title_full_unstemmed Age-Dependent Shift of AMPA Receptors From Synapses to Intracellular Compartments in Alzheimer’s Disease: Immunocytochemical Analysis of the CA1 Hippocampal Region in APP/PS1 Transgenic Mouse Model
title_short Age-Dependent Shift of AMPA Receptors From Synapses to Intracellular Compartments in Alzheimer’s Disease: Immunocytochemical Analysis of the CA1 Hippocampal Region in APP/PS1 Transgenic Mouse Model
title_sort age-dependent shift of ampa receptors from synapses to intracellular compartments in alzheimer’s disease: immunocytochemical analysis of the ca1 hippocampal region in app/ps1 transgenic mouse model
topic Neuroscience
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7572859/
https://www.ncbi.nlm.nih.gov/pubmed/33132900
http://dx.doi.org/10.3389/fnagi.2020.577996
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