Reduction in the neuronal surface of post and presynaptic GABAB receptors in the hippocampus in a mouse model of Alzheimer’s disease

The hippocampus plays key roles in learning and memory and is a main target of Alzheimer’s disease (AD), which causes progressive memory impairments. Despite numerous investigations about the processes required for the normal hippocampal functions, the neurotransmitter receptors involved in the syna...

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Autores: Martín Belmonte, Alejandro, Aguado Rubio, Carolina, Alfaro Ruiz, Rocío, Moreno Martínez, Ana Esther, Ossa, Luis de la, Martínez Hernández, José, Buisson, Alain, Früh, Simon, Bettler, Bernhard, Shigemoto, Ryuichi, Fukazawa, Yugo, Luján Miras, Rafael
Tipo de recurso: artículo
Fecha de publicación:2019
País:España
Institución:Universidad de Castilla-La Mancha
Repositorio:RUIdeRA. Repositorio Institucional de la UCLM
OAI Identifier:oai:ruidera.uclm.es:10578/23760
Acceso en línea:https://hdl.handle.net/10578/23760
Access Level:acceso abierto
Palabra clave:Alzheimer's disease
Electron microscopy
Freeze-fracture
GABAB receptors
Hippocampus
Immunohistochemistry
Ion channels
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spelling Reduction in the neuronal surface of post and presynaptic GABAB receptors in the hippocampus in a mouse model of Alzheimer’s diseaseMartín Belmonte, AlejandroAguado Rubio, CarolinaAlfaro Ruiz, RocíoMoreno Martínez, Ana EstherOssa, Luis de laMartínez Hernández, JoséBuisson, AlainFrüh, SimonBettler, BernhardShigemoto, RyuichiFukazawa, YugoLuján Miras, RafaelAlzheimer's diseaseElectron microscopyFreeze-fractureGABAB receptorsHippocampusImmunohistochemistryIon channelsThe hippocampus plays key roles in learning and memory and is a main target of Alzheimer’s disease (AD), which causes progressive memory impairments. Despite numerous investigations about the processes required for the normal hippocampal functions, the neurotransmitter receptors involved in the synaptic deficits by which AD disables the hippocampus are not yet characterized. By combining histoblots, western blots, immunohistochemistry and high-resolution immunoelectron microscopic methods for GABAB receptors, this study provides a quantitative description of the expression and the subcellular localization of GABAB1 in the hippocampus in a mouse model of AD at 1, 6 and 12 months of age. Western blots and histoblots showed that the total amount of protein and the laminar expression pattern of GABAB1 were similar in APP/PS1 mice and in age-matched wild-type mice. In contrast, immunoelectron microscopic techniques showed that the subcellular localization of GABAB1 subunit did not change significantly in APP/PS1 mice at 1 month of age, was significantly reduced in the stratum lacunosum-moleculare of CA1 pyramidal cells at 6 months of age and significantly reduced at the membrane surface of CA1 pyramidal cells at 12 months of age. This reduction of plasma membrane GABAB1 was paralleled by a significant increase of the subunit at the intracellular sites. We further observed a decrease of membrane-targeted GABAB receptors in axon terminals contacting CA1 pyramidal cells. Our data demonstrate compartment- and age-dependent reduction of plasma membrane-targeted GABAB receptors in the CA1 region of the hippocampus, suggesting that this decrease might be enough to alter the GABAB-mediated synaptic transmission taking place in AD.Wiley202020202019info:eu-repo/semantics/articleapplication/pdfapplication/pdfhttps://hdl.handle.net/10578/23760reponame:RUIdeRA. Repositorio Institucional de la UCLMinstname:Universidad de Castilla-La ManchaInglésinfo:eu-repo/semantics/openAccessoai:ruidera.uclm.es:10578/237602026-05-27T07:36:41Z
dc.title.none.fl_str_mv Reduction in the neuronal surface of post and presynaptic GABAB receptors in the hippocampus in a mouse model of Alzheimer’s disease
title Reduction in the neuronal surface of post and presynaptic GABAB receptors in the hippocampus in a mouse model of Alzheimer’s disease
spellingShingle Reduction in the neuronal surface of post and presynaptic GABAB receptors in the hippocampus in a mouse model of Alzheimer’s disease
Martín Belmonte, Alejandro
Alzheimer's disease
Electron microscopy
Freeze-fracture
GABAB receptors
Hippocampus
Immunohistochemistry
Ion channels
title_short Reduction in the neuronal surface of post and presynaptic GABAB receptors in the hippocampus in a mouse model of Alzheimer’s disease
title_full Reduction in the neuronal surface of post and presynaptic GABAB receptors in the hippocampus in a mouse model of Alzheimer’s disease
title_fullStr Reduction in the neuronal surface of post and presynaptic GABAB receptors in the hippocampus in a mouse model of Alzheimer’s disease
title_full_unstemmed Reduction in the neuronal surface of post and presynaptic GABAB receptors in the hippocampus in a mouse model of Alzheimer’s disease
title_sort Reduction in the neuronal surface of post and presynaptic GABAB receptors in the hippocampus in a mouse model of Alzheimer’s disease
dc.creator.none.fl_str_mv Martín Belmonte, Alejandro
Aguado Rubio, Carolina
Alfaro Ruiz, Rocío
Moreno Martínez, Ana Esther
Ossa, Luis de la
Martínez Hernández, José
Buisson, Alain
Früh, Simon
Bettler, Bernhard
Shigemoto, Ryuichi
Fukazawa, Yugo
Luján Miras, Rafael
author Martín Belmonte, Alejandro
author_facet Martín Belmonte, Alejandro
Aguado Rubio, Carolina
Alfaro Ruiz, Rocío
Moreno Martínez, Ana Esther
Ossa, Luis de la
Martínez Hernández, José
Buisson, Alain
Früh, Simon
Bettler, Bernhard
Shigemoto, Ryuichi
Fukazawa, Yugo
Luján Miras, Rafael
author_role author
author2 Aguado Rubio, Carolina
Alfaro Ruiz, Rocío
Moreno Martínez, Ana Esther
Ossa, Luis de la
Martínez Hernández, José
Buisson, Alain
Früh, Simon
Bettler, Bernhard
Shigemoto, Ryuichi
Fukazawa, Yugo
Luján Miras, Rafael
author2_role author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Alzheimer's disease
Electron microscopy
Freeze-fracture
GABAB receptors
Hippocampus
Immunohistochemistry
Ion channels
topic Alzheimer's disease
Electron microscopy
Freeze-fracture
GABAB receptors
Hippocampus
Immunohistochemistry
Ion channels
description The hippocampus plays key roles in learning and memory and is a main target of Alzheimer’s disease (AD), which causes progressive memory impairments. Despite numerous investigations about the processes required for the normal hippocampal functions, the neurotransmitter receptors involved in the synaptic deficits by which AD disables the hippocampus are not yet characterized. By combining histoblots, western blots, immunohistochemistry and high-resolution immunoelectron microscopic methods for GABAB receptors, this study provides a quantitative description of the expression and the subcellular localization of GABAB1 in the hippocampus in a mouse model of AD at 1, 6 and 12 months of age. Western blots and histoblots showed that the total amount of protein and the laminar expression pattern of GABAB1 were similar in APP/PS1 mice and in age-matched wild-type mice. In contrast, immunoelectron microscopic techniques showed that the subcellular localization of GABAB1 subunit did not change significantly in APP/PS1 mice at 1 month of age, was significantly reduced in the stratum lacunosum-moleculare of CA1 pyramidal cells at 6 months of age and significantly reduced at the membrane surface of CA1 pyramidal cells at 12 months of age. This reduction of plasma membrane GABAB1 was paralleled by a significant increase of the subunit at the intracellular sites. We further observed a decrease of membrane-targeted GABAB receptors in axon terminals contacting CA1 pyramidal cells. Our data demonstrate compartment- and age-dependent reduction of plasma membrane-targeted GABAB receptors in the CA1 region of the hippocampus, suggesting that this decrease might be enough to alter the GABAB-mediated synaptic transmission taking place in AD.
publishDate 2019
dc.date.none.fl_str_mv 2019
2020
2020
dc.type.none.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv https://hdl.handle.net/10578/23760
url https://hdl.handle.net/10578/23760
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Wiley
publisher.none.fl_str_mv Wiley
dc.source.none.fl_str_mv reponame:RUIdeRA. Repositorio Institucional de la UCLM
instname:Universidad de Castilla-La Mancha
instname_str Universidad de Castilla-La Mancha
reponame_str RUIdeRA. Repositorio Institucional de la UCLM
collection RUIdeRA. Repositorio Institucional de la UCLM
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15.300719

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