The influence of phospho-tau on dendritic spines of cortical pyramidal neurons in patients with Alzheimer's disease

The dendritic spines on pyramidal cells represent the main postsynaptic elements of cortical excitatory synapses and they are fundamental structures in memory, learning and cognition. In the present study, we used intracellular injections of Lucifer yellow in fixed tissue to analyse over 19 500 dend...

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Detalhes bibliográficos
Autores: Merino-Serrais, Paula, Benavides-Piccione, Ruth, Blázquez-Llorca, Lidia, Kastanauskaite, Asta, Rábano, Alberto, Ávila, Jesús, DeFelipe, Javier
Formato: artículo
Estado:Versión publicada
Fecha de publicación:2013
País:España
Recursos:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/252288
Acesso em linha:http://hdl.handle.net/10261/252288
Access Level:acceso abierto
Palavra-chave:Intracellular injection
Hippocampal formation
Dendritic spine density and volume
3D-reconstruction
Confocal
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spelling The influence of phospho-tau on dendritic spines of cortical pyramidal neurons in patients with Alzheimer's diseaseMerino-Serrais, PaulaBenavides-Piccione, RuthBlázquez-Llorca, LidiaKastanauskaite, AstaRábano, AlbertoÁvila, JesúsDeFelipe, JavierIntracellular injectionHippocampal formationDendritic spine density and volume3D-reconstructionConfocalThe dendritic spines on pyramidal cells represent the main postsynaptic elements of cortical excitatory synapses and they are fundamental structures in memory, learning and cognition. In the present study, we used intracellular injections of Lucifer yellow in fixed tissue to analyse over 19 500 dendritic spines that were completely reconstructed in three dimensions along the length of the basal dendrites of pyramidal neurons in the parahippocampal cortex and CA1 of patients with Alzheimer's disease. Following intracellular injection, sections were immunostained for anti-Lucifer yellow and with tau monoclonal antibodies AT8 and PHF-1, which recognize tau phosphorylated at Ser202/Thr205 and at Ser396/404, respectively. We observed that the diffuse accumulation of phospho-tau in a putative pre-tangle state did not induce changes in the dendrites of pyramidal neurons, whereas the presence of tau aggregates forming intraneuronal neurofibrillary tangles was associated with progressive alteration of dendritic spines (loss of dendritic spines and changes in their morphology) and dendrite atrophy, depending on the degree of tangle development. Thus, the presence of phospho-tau in neurons does not necessarily mean that they suffer severe and irreversible effects as thought previously but rather, the characteristic cognitive impairment in Alzheimer's disease is likely to depend on the relative number of neurons that have well developed tangles. © 2013 The Author.CIBERNED (CB06/05/0066), Fundación CIEN (Financiación de Proyectos de Investigación de Enfermedad de Alzheimer enfermedades relacionadas 2008), Fundación Caixa (BM05-47-0) and the Spanish Ministry of Economy and Competitiveness (SAF2009-09394 and BFU2012-34963).Oxford University PressCentro Investigación Biomédica en Red Enfermedades Neurodegenerativas (España)Fundación Centro de Investigación de Enfermedades NeurológicasLa CaixaMinisterio de Economía y Competitividad (España)Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]2021202120132021info:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_6501Publisher's versioninfo:eu-repo/semantics/publishedVersionhttp://hdl.handle.net/10261/252288reponame:DIGITAL.CSIC. Repositorio Institucional del CSICinstname:Consejo Superior de Investigaciones Científicas (CSIC)Ingléshttp://dx.doi.org/10.1093/brain/awt088Síinfo:eu-repo/semantics/openAccessoai:digital.csic.es:10261/2522882026-05-22T06:33:51Z
dc.title.none.fl_str_mv The influence of phospho-tau on dendritic spines of cortical pyramidal neurons in patients with Alzheimer's disease
title The influence of phospho-tau on dendritic spines of cortical pyramidal neurons in patients with Alzheimer's disease
spellingShingle The influence of phospho-tau on dendritic spines of cortical pyramidal neurons in patients with Alzheimer's disease
Merino-Serrais, Paula
Intracellular injection
Hippocampal formation
Dendritic spine density and volume
3D-reconstruction
Confocal
title_short The influence of phospho-tau on dendritic spines of cortical pyramidal neurons in patients with Alzheimer's disease
title_full The influence of phospho-tau on dendritic spines of cortical pyramidal neurons in patients with Alzheimer's disease
title_fullStr The influence of phospho-tau on dendritic spines of cortical pyramidal neurons in patients with Alzheimer's disease
title_full_unstemmed The influence of phospho-tau on dendritic spines of cortical pyramidal neurons in patients with Alzheimer's disease
title_sort The influence of phospho-tau on dendritic spines of cortical pyramidal neurons in patients with Alzheimer's disease
dc.creator.none.fl_str_mv Merino-Serrais, Paula
Benavides-Piccione, Ruth
Blázquez-Llorca, Lidia
Kastanauskaite, Asta
Rábano, Alberto
Ávila, Jesús
DeFelipe, Javier
author Merino-Serrais, Paula
author_facet Merino-Serrais, Paula
Benavides-Piccione, Ruth
Blázquez-Llorca, Lidia
Kastanauskaite, Asta
Rábano, Alberto
Ávila, Jesús
DeFelipe, Javier
author_role author
author2 Benavides-Piccione, Ruth
Blázquez-Llorca, Lidia
Kastanauskaite, Asta
Rábano, Alberto
Ávila, Jesús
DeFelipe, Javier
author2_role author
author
author
author
author
author
dc.contributor.none.fl_str_mv Centro Investigación Biomédica en Red Enfermedades Neurodegenerativas (España)
Fundación Centro de Investigación de Enfermedades Neurológicas
La Caixa
Ministerio de Economía y Competitividad (España)
Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]
dc.subject.none.fl_str_mv Intracellular injection
Hippocampal formation
Dendritic spine density and volume
3D-reconstruction
Confocal
topic Intracellular injection
Hippocampal formation
Dendritic spine density and volume
3D-reconstruction
Confocal
description The dendritic spines on pyramidal cells represent the main postsynaptic elements of cortical excitatory synapses and they are fundamental structures in memory, learning and cognition. In the present study, we used intracellular injections of Lucifer yellow in fixed tissue to analyse over 19 500 dendritic spines that were completely reconstructed in three dimensions along the length of the basal dendrites of pyramidal neurons in the parahippocampal cortex and CA1 of patients with Alzheimer's disease. Following intracellular injection, sections were immunostained for anti-Lucifer yellow and with tau monoclonal antibodies AT8 and PHF-1, which recognize tau phosphorylated at Ser202/Thr205 and at Ser396/404, respectively. We observed that the diffuse accumulation of phospho-tau in a putative pre-tangle state did not induce changes in the dendrites of pyramidal neurons, whereas the presence of tau aggregates forming intraneuronal neurofibrillary tangles was associated with progressive alteration of dendritic spines (loss of dendritic spines and changes in their morphology) and dendrite atrophy, depending on the degree of tangle development. Thus, the presence of phospho-tau in neurons does not necessarily mean that they suffer severe and irreversible effects as thought previously but rather, the characteristic cognitive impairment in Alzheimer's disease is likely to depend on the relative number of neurons that have well developed tangles. © 2013 The Author.
publishDate 2013
dc.date.none.fl_str_mv 2013
2021
2021
2021
dc.type.none.fl_str_mv info:eu-repo/semantics/article
http://purl.org/coar/resource_type/c_6501
Publisher's version
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10261/252288
url http://hdl.handle.net/10261/252288
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv http://dx.doi.org/10.1093/brain/awt088
Sí
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv Oxford University Press
publisher.none.fl_str_mv Oxford University Press
dc.source.none.fl_str_mv reponame:DIGITAL.CSIC. Repositorio Institucional del CSIC
instname:Consejo Superior de Investigaciones Científicas (CSIC)
instname_str Consejo Superior de Investigaciones Científicas (CSIC)
reponame_str DIGITAL.CSIC. Repositorio Institucional del CSIC
collection DIGITAL.CSIC. Repositorio Institucional del CSIC
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,81155

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