Different modes of synaptic and extrasynaptic NMDA receptor alteration in the hippocampus of P301S tau transgenic mice

N-methyl-d-aspartate receptors (NMDARs) are pivotal players in the synaptic transmission and synaptic plasticity underlying learning and memory. Accordingly, dysfunction of NMDARs has been implicated in the pathophysiology of Alzheimer disease (AD). Here, we used histoblot and sodium dodecylsulphate...

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Autores: Alfaro Ruiz, Rocío, Aguado Rubio, Carolina, Martin Belmonte, Alejandro, Moreno Martínez, Ana Esther, Merchán Rubira, Jesús, Hernández , Félix, Ávila , Jesús, Fukazawa , Yugo, Luján Miras, Rafael
Formato: artículo
Fecha de publicación:2022
País:España
Recursos:Universidad de Castilla-La Mancha
Repositorio:RUIdeRA. Repositorio Institucional de la UCLM
OAI Identifier:oai:ruidera.uclm.es:10578/40638
Acesso em linha:https://hdl.handle.net/10578/40638
Access Level:acceso abierto
Palavra-chave:AD mouse model
Alzheimer disease
Electron microscopy
Freeze-fracture
Hippocampus
Immunohistochemistry
NMDA receptors
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spelling Different modes of synaptic and extrasynaptic NMDA receptor alteration in the hippocampus of P301S tau transgenic miceAlfaro Ruiz, RocíoAguado Rubio, CarolinaMartin Belmonte, AlejandroMoreno Martínez, Ana EstherMerchán Rubira, JesúsHernández , FélixÁvila , JesúsFukazawa , YugoLuján Miras, RafaelAD mouse modelAlzheimer diseaseElectron microscopyFreeze-fractureHippocampusImmunohistochemistryNMDA receptorsN-methyl-d-aspartate receptors (NMDARs) are pivotal players in the synaptic transmission and synaptic plasticity underlying learning and memory. Accordingly, dysfunction of NMDARs has been implicated in the pathophysiology of Alzheimer disease (AD). Here, we used histoblot and sodium dodecylsulphate-digested freeze-fracture replica labelling (SDS-FRL) techniques to investigate the expression and subcellular localisation of GluN1, the obligatory subunit of NMDARs, in the hippocampus of P301S mice. Histoblots showed that GluN1 expression was significantly reduced in the hippocampus of P301S mice in a laminar-specific manner at 10 months of age but was unaltered at 3 months. Using the SDS-FRL technique, excitatory synapses and extrasynaptic sites on spines of pyramidal cells and interneuron dendrites were analysed throughout all dendritic layers in the CA1 field. Our ultrastructural approach revealed a high density of GluN1 in synaptic sites and a substantially lower density at extrasynaptic sites. Labelling density for GluN1 in excitatory synapses established on spines was significantly reduced in P301S mice, compared with age-matched wild-type mice, in the stratum oriens (so), stratum radiatum (sr) and stratum lacunosum-moleculare (slm). Density for synaptic GluN1 on interneuron dendrites was significantly reduced in P301S mice in the so and sr but unaltered in the slm. Labelling density for GluN1 at extrasynaptic sites showed no significant differences in pyramidal cells, and only increased density in the interneuron dendrites of the sr. This differential alteration of synaptic versus extrasynaptic NMDARs supports the notion that the progressive accumulation of phospho-tau is associated with changes in NMDARs, in the absence of amyloid-ß pathology, and may be involved in the mechanisms causing abnormal network activity of the hippocampal circuit.Wiley202520252022info:eu-repo/semantics/articleapplication/pdfapplication/pdfhttps://hdl.handle.net/10578/40638reponame:RUIdeRA. Repositorio Institucional de la UCLMinstname:Universidad de Castilla-La ManchaInglésSBPLY/17/180501/000229PID2021-125875OB-I00RTI2018-095812-B100SBPLY/21/180501/000064Grant/Award Numbers: 16H04662, 19H03323, 20H05058info:eu-repo/semantics/openAccessoai:ruidera.uclm.es:10578/406382026-05-27T07:36:41Z
dc.title.none.fl_str_mv Different modes of synaptic and extrasynaptic NMDA receptor alteration in the hippocampus of P301S tau transgenic mice
title Different modes of synaptic and extrasynaptic NMDA receptor alteration in the hippocampus of P301S tau transgenic mice
spellingShingle Different modes of synaptic and extrasynaptic NMDA receptor alteration in the hippocampus of P301S tau transgenic mice
Alfaro Ruiz, Rocío
AD mouse model
Alzheimer disease
Electron microscopy
Freeze-fracture
Hippocampus
Immunohistochemistry
NMDA receptors
title_short Different modes of synaptic and extrasynaptic NMDA receptor alteration in the hippocampus of P301S tau transgenic mice
title_full Different modes of synaptic and extrasynaptic NMDA receptor alteration in the hippocampus of P301S tau transgenic mice
title_fullStr Different modes of synaptic and extrasynaptic NMDA receptor alteration in the hippocampus of P301S tau transgenic mice
title_full_unstemmed Different modes of synaptic and extrasynaptic NMDA receptor alteration in the hippocampus of P301S tau transgenic mice
title_sort Different modes of synaptic and extrasynaptic NMDA receptor alteration in the hippocampus of P301S tau transgenic mice
dc.creator.none.fl_str_mv Alfaro Ruiz, Rocío
Aguado Rubio, Carolina
Martin Belmonte, Alejandro
Moreno Martínez, Ana Esther
Merchán Rubira, Jesús
Hernández , Félix
Ávila , Jesús
Fukazawa , Yugo
Luján Miras, Rafael
author Alfaro Ruiz, Rocío
author_facet Alfaro Ruiz, Rocío
Aguado Rubio, Carolina
Martin Belmonte, Alejandro
Moreno Martínez, Ana Esther
Merchán Rubira, Jesús
Hernández , Félix
Ávila , Jesús
Fukazawa , Yugo
Luján Miras, Rafael
author_role author
author2 Aguado Rubio, Carolina
Martin Belmonte, Alejandro
Moreno Martínez, Ana Esther
Merchán Rubira, Jesús
Hernández , Félix
Ávila , Jesús
Fukazawa , Yugo
Luján Miras, Rafael
author2_role author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv AD mouse model
Alzheimer disease
Electron microscopy
Freeze-fracture
Hippocampus
Immunohistochemistry
NMDA receptors
topic AD mouse model
Alzheimer disease
Electron microscopy
Freeze-fracture
Hippocampus
Immunohistochemistry
NMDA receptors
description N-methyl-d-aspartate receptors (NMDARs) are pivotal players in the synaptic transmission and synaptic plasticity underlying learning and memory. Accordingly, dysfunction of NMDARs has been implicated in the pathophysiology of Alzheimer disease (AD). Here, we used histoblot and sodium dodecylsulphate-digested freeze-fracture replica labelling (SDS-FRL) techniques to investigate the expression and subcellular localisation of GluN1, the obligatory subunit of NMDARs, in the hippocampus of P301S mice. Histoblots showed that GluN1 expression was significantly reduced in the hippocampus of P301S mice in a laminar-specific manner at 10 months of age but was unaltered at 3 months. Using the SDS-FRL technique, excitatory synapses and extrasynaptic sites on spines of pyramidal cells and interneuron dendrites were analysed throughout all dendritic layers in the CA1 field. Our ultrastructural approach revealed a high density of GluN1 in synaptic sites and a substantially lower density at extrasynaptic sites. Labelling density for GluN1 in excitatory synapses established on spines was significantly reduced in P301S mice, compared with age-matched wild-type mice, in the stratum oriens (so), stratum radiatum (sr) and stratum lacunosum-moleculare (slm). Density for synaptic GluN1 on interneuron dendrites was significantly reduced in P301S mice in the so and sr but unaltered in the slm. Labelling density for GluN1 at extrasynaptic sites showed no significant differences in pyramidal cells, and only increased density in the interneuron dendrites of the sr. This differential alteration of synaptic versus extrasynaptic NMDARs supports the notion that the progressive accumulation of phospho-tau is associated with changes in NMDARs, in the absence of amyloid-ß pathology, and may be involved in the mechanisms causing abnormal network activity of the hippocampal circuit.
publishDate 2022
dc.date.none.fl_str_mv 2022
2025
2025
dc.type.none.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv https://hdl.handle.net/10578/40638
url https://hdl.handle.net/10578/40638
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv SBPLY/17/180501/000229
PID2021-125875OB-I00
RTI2018-095812-B100
SBPLY/21/180501/000064
Grant/Award Numbers: 16H04662, 19H03323, 20H05058
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 15,228081

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