Increase in the density of resting microglia precedes neuritic plaque formation and microglial activation in a transgenic model of Alzheimer's disease

The formation of cerebral senile plaques composed of amyloid beta peptide (A beta) is a fundamental feature of Alzheimer's disease (AD). Glial cells and more specifically microglia become reactive in the presence of A beta. In a triple transgenic model of AD (3 x Tg-AD), we found a significant...

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Autores: Rodríguez Arellano, José Julio, Witton, J., Olabarria, M., Noristani, H.N., Verkhratsky, Alexei
Formato: artículo
Fecha de publicación:2010
País:España
Recursos:Universidad del País Vasco
Repositorio:Addi. Archivo Digital para la Docencia y la Investigación
OAI Identifier:oai:addi.ehu.eus:10810/11884
Acesso em linha:http://hdl.handle.net/10810/11884
Access Level:acceso abierto
Palavra-chave:microglia
Alzheimer's disease
hippocampus
plasticity
beta-amyloid
mouse model
in-vivo
inflammatory response
amyloid plaques
A beta
brain
cells
mice
system
dysfunction
CELL BIOLOGY
ONCOLOGY
MEDICINE
IMMUNOLOGY AND MICROBIOLOGY
CELLULAR AND MOLECULAR NEUROSCIENCE
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oai_identifier_str oai:addi.ehu.eus:10810/11884
network_acronym_str ES
network_name_str España
repository_id_str
spelling Increase in the density of resting microglia precedes neuritic plaque formation and microglial activation in a transgenic model of Alzheimer's diseaseRodríguez Arellano, José JulioWitton, J.Olabarria, M.Noristani, H.N.Verkhratsky, AlexeimicrogliaAlzheimer's diseasehippocampusplasticitybeta-amyloidmouse modelin-vivoinflammatory responseamyloid plaquesA betabraincellsmicesystemdysfunctionCELL BIOLOGYONCOLOGYMEDICINEIMMUNOLOGY AND MICROBIOLOGYCELLULAR AND MOLECULAR NEUROSCIENCEThe formation of cerebral senile plaques composed of amyloid beta peptide (A beta) is a fundamental feature of Alzheimer's disease (AD). Glial cells and more specifically microglia become reactive in the presence of A beta. In a triple transgenic model of AD (3 x Tg-AD), we found a significant increase in activated microglia at 12 (by 111%) and 18 (by 88%) months of age when compared with non-transgenic (non-Tg) controls. This microglial activation correlated with A beta plaque formation, and the activation in microglia was closely associated with A beta plaques and smaller A beta deposits. We also found a significant increase in the area density of resting microglia in 3 x Tg-AD animals both at plaque-free stage (at 9 months by 105%) and after the development of A plaques (at 12 months by 54% and at 18 months by 131%). Our results show for the first time that the increase in the density of resting microglia precedes both plaque formation and activation of microglia by extracellular A beta accumulation. We suggest that AD pathology triggers a complex microglial reaction: at the initial stages of the disease the number of resting microglia increases, as if in preparation for the ensuing activation in an attempt to fight the extracellular A beta load that is characteristic of the terminal stages of the disease. Cell Death and Disease (2010) 1, e1; doi:10.1038/cddis.2009.2; published online 14 January 2010Supported by the Alzheimer's Research Trust (UK) Programme Grant ART/PG2004A/1 to AV and JJR; and the Grant Agency of the Czech Republic GACR 309/09/1696 to JJR and GACR 305/08/1384 to AV.Nature Publishing Group201420142010info:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10810/11884reponame:Addi. Archivo Digital para la Docencia y la Investigacióninstname:Universidad del País VascoIngléshttp://www.nature.com/cddis/journal/v1/n1/full/cddis20092a.htmlinfo:eu-repo/semantics/openAccessThis is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits distribution and reproduction in any medium, provided the original author and source are credited. This license does not permit commercial exploitation without specific permission.oai:addi.ehu.eus:10810/118842026-06-18T09:23:17Z
dc.title.none.fl_str_mv Increase in the density of resting microglia precedes neuritic plaque formation and microglial activation in a transgenic model of Alzheimer's disease
title Increase in the density of resting microglia precedes neuritic plaque formation and microglial activation in a transgenic model of Alzheimer's disease
spellingShingle Increase in the density of resting microglia precedes neuritic plaque formation and microglial activation in a transgenic model of Alzheimer's disease
Rodríguez Arellano, José Julio
microglia
Alzheimer's disease
hippocampus
plasticity
beta-amyloid
mouse model
in-vivo
inflammatory response
amyloid plaques
A beta
brain
cells
mice
system
dysfunction
CELL BIOLOGY
ONCOLOGY
MEDICINE
IMMUNOLOGY AND MICROBIOLOGY
CELLULAR AND MOLECULAR NEUROSCIENCE
title_short Increase in the density of resting microglia precedes neuritic plaque formation and microglial activation in a transgenic model of Alzheimer's disease
title_full Increase in the density of resting microglia precedes neuritic plaque formation and microglial activation in a transgenic model of Alzheimer's disease
title_fullStr Increase in the density of resting microglia precedes neuritic plaque formation and microglial activation in a transgenic model of Alzheimer's disease
title_full_unstemmed Increase in the density of resting microglia precedes neuritic plaque formation and microglial activation in a transgenic model of Alzheimer's disease
title_sort Increase in the density of resting microglia precedes neuritic plaque formation and microglial activation in a transgenic model of Alzheimer's disease
dc.creator.none.fl_str_mv Rodríguez Arellano, José Julio
Witton, J.
Olabarria, M.
Noristani, H.N.
Verkhratsky, Alexei
author Rodríguez Arellano, José Julio
author_facet Rodríguez Arellano, José Julio
Witton, J.
Olabarria, M.
Noristani, H.N.
Verkhratsky, Alexei
author_role author
author2 Witton, J.
Olabarria, M.
Noristani, H.N.
Verkhratsky, Alexei
author2_role author
author
author
author
dc.subject.none.fl_str_mv microglia
Alzheimer's disease
hippocampus
plasticity
beta-amyloid
mouse model
in-vivo
inflammatory response
amyloid plaques
A beta
brain
cells
mice
system
dysfunction
CELL BIOLOGY
ONCOLOGY
MEDICINE
IMMUNOLOGY AND MICROBIOLOGY
CELLULAR AND MOLECULAR NEUROSCIENCE
topic microglia
Alzheimer's disease
hippocampus
plasticity
beta-amyloid
mouse model
in-vivo
inflammatory response
amyloid plaques
A beta
brain
cells
mice
system
dysfunction
CELL BIOLOGY
ONCOLOGY
MEDICINE
IMMUNOLOGY AND MICROBIOLOGY
CELLULAR AND MOLECULAR NEUROSCIENCE
description The formation of cerebral senile plaques composed of amyloid beta peptide (A beta) is a fundamental feature of Alzheimer's disease (AD). Glial cells and more specifically microglia become reactive in the presence of A beta. In a triple transgenic model of AD (3 x Tg-AD), we found a significant increase in activated microglia at 12 (by 111%) and 18 (by 88%) months of age when compared with non-transgenic (non-Tg) controls. This microglial activation correlated with A beta plaque formation, and the activation in microglia was closely associated with A beta plaques and smaller A beta deposits. We also found a significant increase in the area density of resting microglia in 3 x Tg-AD animals both at plaque-free stage (at 9 months by 105%) and after the development of A plaques (at 12 months by 54% and at 18 months by 131%). Our results show for the first time that the increase in the density of resting microglia precedes both plaque formation and activation of microglia by extracellular A beta accumulation. We suggest that AD pathology triggers a complex microglial reaction: at the initial stages of the disease the number of resting microglia increases, as if in preparation for the ensuing activation in an attempt to fight the extracellular A beta load that is characteristic of the terminal stages of the disease. Cell Death and Disease (2010) 1, e1; doi:10.1038/cddis.2009.2; published online 14 January 2010
publishDate 2010
dc.date.none.fl_str_mv 2010
2014
2014
dc.type.none.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv http://hdl.handle.net/10810/11884
url http://hdl.handle.net/10810/11884
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv http://www.nature.com/cddis/journal/v1/n1/full/cddis20092a.html
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Nature Publishing Group
publisher.none.fl_str_mv Nature Publishing Group
dc.source.none.fl_str_mv reponame:Addi. Archivo Digital para la Docencia y la Investigación
instname:Universidad del País Vasco
instname_str Universidad del País Vasco
reponame_str Addi. Archivo Digital para la Docencia y la Investigación
collection Addi. Archivo Digital para la Docencia y la Investigación
repository.name.fl_str_mv
repository.mail.fl_str_mv
_version_ 1869404298806296576
score 15.198674

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