Age-dependent decrease in glutamine synthetase expression in the hippocampal astroglia of the triple transgenic Alzheimer's disease mouse model : mechanism for deficient glutamatergic transmission?

Astrocytes are fundamental for brain homeostasis and the progression and outcome of many neuropathologies including Alzheimer's disease (AD). In the triple transgenic mouse model of AD (3xTg-AD) generalised hippocampal astroglia atrophy precedes a restricted and specific beta-amyloid (A beta) p...

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Autores: Olabarria, Markel, Noristani, Harun N., Verkhratsky, Alexei, Rodríguez Arellano, José Julio
Formato: artículo
Fecha de publicación:2011
País:España
Recursos:Universidad del País Vasco
Repositorio:Addi. Archivo Digital para la Docencia y la Investigación
OAI Identifier:oai:addi.ehu.eus:10810/7325
Acesso em linha:http://hdl.handle.net/10810/7325
Access Level:acceso abierto
Palavra-chave:astroglia
Alzheimer's disease
glutamine synthetase
GFAP
amyloid beta
excitotoxicity
hippocampus
plasticity
CELLULAR AND MOLECULAR NEUROSCIENCE
NEUROLOGY
MOLECULAR BIOLOGY
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spelling Age-dependent decrease in glutamine synthetase expression in the hippocampal astroglia of the triple transgenic Alzheimer's disease mouse model : mechanism for deficient glutamatergic transmission?Olabarria, MarkelNoristani, Harun N.Verkhratsky, AlexeiRodríguez Arellano, José JulioastrogliaAlzheimer's diseaseglutamine synthetaseGFAPamyloid betaexcitotoxicityhippocampusplasticityCELLULAR AND MOLECULAR NEUROSCIENCENEUROLOGYMOLECULAR BIOLOGYAstrocytes are fundamental for brain homeostasis and the progression and outcome of many neuropathologies including Alzheimer's disease (AD). In the triple transgenic mouse model of AD (3xTg-AD) generalised hippocampal astroglia atrophy precedes a restricted and specific beta-amyloid (A beta) plaque-related astrogliosis. Astrocytes are critical for CNS glutamatergic transmission being the principal elements of glutamate homeostasis through maintaining its synthesis, uptake and turnover via glutamate-glutamine shuttle. Glutamine synthetase (GS), which is specifically expressed in astrocytes, forms glutamine by an ATP-dependent amination of glutamate. Here, we report changes in GS astrocytic expression in two major cognitive areas of the hippocampus (the dentate gyrus, DG and the CA1) in 3xTg-AD animals aged between 9 and 18 months. We found a significant reduction in Nv (number of cell/mm(3)) of GS immunoreactive (GS-IR) astrocytes starting from 12 months (28.59%) of age in the DG, and sustained at 18 months (31.65%). CA1 decrease of GS-positive astrocytes Nv (33.26%) occurs at 18 months. This Nv reduction of GSIR astrocytes is paralleled by a decrease in overall GS expression (determined by its optical density) that becomes significant at 18 months (21.61% and 19.68% in DG and CA1, respectively). GS-IR Nv changes are directly associated with the presence of A beta deposits showing a decrease of 47.92% as opposed to 23.47% in areas free of A beta. These changes in GS containing astrocytes and GS-immunoreactivity indicate AD-related impairments of glutamate homeostatic system, at the advanced and late stages of the disease, which may affect the efficacy of glutamatergic transmission in the diseased brain that may contribute to the cognitive deficiency.The present study was supported by Alzheimer's Research Trust Programme Grant (ART/PG2004A/1) to JJR and AV. Grant Agency of the Czech Republic (GACR 309/09/1696 and GACR 304/11/0184) to JJR and (GACR 305/08/1381; GACR 305/08/1384) to AV. The Spanish Government, Plan Nacional de I+D+I 2008-2011 and ISCIII-Subdireccion General de Evaluacion y Fomento de la investigacion (PI10/02738) to JJR and AV and the Government of the Basque Country grant (AE-2010-1-28; AEGV10/16) to JJR. The authors would also like to thank BBSRC for the Ph.D. studentship to H.N. Noristani.BioMed Central201220122011info:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10810/7325reponame:Addi. Archivo Digital para la Docencia y la Investigacióninstname:Universidad del País VascoIngléshttp://www.molecularneurodegeneration.com/content/6/1/55info:eu-repo/semantics/openAccess© 2011 Olabarria et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.oai:addi.ehu.eus:10810/73252026-06-18T09:23:17Z
dc.title.none.fl_str_mv Age-dependent decrease in glutamine synthetase expression in the hippocampal astroglia of the triple transgenic Alzheimer's disease mouse model : mechanism for deficient glutamatergic transmission?
title Age-dependent decrease in glutamine synthetase expression in the hippocampal astroglia of the triple transgenic Alzheimer's disease mouse model : mechanism for deficient glutamatergic transmission?
spellingShingle Age-dependent decrease in glutamine synthetase expression in the hippocampal astroglia of the triple transgenic Alzheimer's disease mouse model : mechanism for deficient glutamatergic transmission?
Olabarria, Markel
astroglia
Alzheimer's disease
glutamine synthetase
GFAP
amyloid beta
excitotoxicity
hippocampus
plasticity
CELLULAR AND MOLECULAR NEUROSCIENCE
NEUROLOGY
MOLECULAR BIOLOGY
title_short Age-dependent decrease in glutamine synthetase expression in the hippocampal astroglia of the triple transgenic Alzheimer's disease mouse model : mechanism for deficient glutamatergic transmission?
title_full Age-dependent decrease in glutamine synthetase expression in the hippocampal astroglia of the triple transgenic Alzheimer's disease mouse model : mechanism for deficient glutamatergic transmission?
title_fullStr Age-dependent decrease in glutamine synthetase expression in the hippocampal astroglia of the triple transgenic Alzheimer's disease mouse model : mechanism for deficient glutamatergic transmission?
title_full_unstemmed Age-dependent decrease in glutamine synthetase expression in the hippocampal astroglia of the triple transgenic Alzheimer's disease mouse model : mechanism for deficient glutamatergic transmission?
title_sort Age-dependent decrease in glutamine synthetase expression in the hippocampal astroglia of the triple transgenic Alzheimer's disease mouse model : mechanism for deficient glutamatergic transmission?
dc.creator.none.fl_str_mv Olabarria, Markel
Noristani, Harun N.
Verkhratsky, Alexei
Rodríguez Arellano, José Julio
author Olabarria, Markel
author_facet Olabarria, Markel
Noristani, Harun N.
Verkhratsky, Alexei
Rodríguez Arellano, José Julio
author_role author
author2 Noristani, Harun N.
Verkhratsky, Alexei
Rodríguez Arellano, José Julio
author2_role author
author
author
dc.subject.none.fl_str_mv astroglia
Alzheimer's disease
glutamine synthetase
GFAP
amyloid beta
excitotoxicity
hippocampus
plasticity
CELLULAR AND MOLECULAR NEUROSCIENCE
NEUROLOGY
MOLECULAR BIOLOGY
topic astroglia
Alzheimer's disease
glutamine synthetase
GFAP
amyloid beta
excitotoxicity
hippocampus
plasticity
CELLULAR AND MOLECULAR NEUROSCIENCE
NEUROLOGY
MOLECULAR BIOLOGY
description Astrocytes are fundamental for brain homeostasis and the progression and outcome of many neuropathologies including Alzheimer's disease (AD). In the triple transgenic mouse model of AD (3xTg-AD) generalised hippocampal astroglia atrophy precedes a restricted and specific beta-amyloid (A beta) plaque-related astrogliosis. Astrocytes are critical for CNS glutamatergic transmission being the principal elements of glutamate homeostasis through maintaining its synthesis, uptake and turnover via glutamate-glutamine shuttle. Glutamine synthetase (GS), which is specifically expressed in astrocytes, forms glutamine by an ATP-dependent amination of glutamate. Here, we report changes in GS astrocytic expression in two major cognitive areas of the hippocampus (the dentate gyrus, DG and the CA1) in 3xTg-AD animals aged between 9 and 18 months. We found a significant reduction in Nv (number of cell/mm(3)) of GS immunoreactive (GS-IR) astrocytes starting from 12 months (28.59%) of age in the DG, and sustained at 18 months (31.65%). CA1 decrease of GS-positive astrocytes Nv (33.26%) occurs at 18 months. This Nv reduction of GSIR astrocytes is paralleled by a decrease in overall GS expression (determined by its optical density) that becomes significant at 18 months (21.61% and 19.68% in DG and CA1, respectively). GS-IR Nv changes are directly associated with the presence of A beta deposits showing a decrease of 47.92% as opposed to 23.47% in areas free of A beta. These changes in GS containing astrocytes and GS-immunoreactivity indicate AD-related impairments of glutamate homeostatic system, at the advanced and late stages of the disease, which may affect the efficacy of glutamatergic transmission in the diseased brain that may contribute to the cognitive deficiency.
publishDate 2011
dc.date.none.fl_str_mv 2011
2012
2012
dc.type.none.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv http://hdl.handle.net/10810/7325
url http://hdl.handle.net/10810/7325
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv http://www.molecularneurodegeneration.com/content/6/1/55
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 BioMed Central
publisher.none.fl_str_mv BioMed Central
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
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score 15,300724

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