Neuronal and glial alterations, increased anxiety, and cognitive impairment before hippocampal amyloid deposition in PDAPP mice, model of Alzheimer's disease

Autores
Beauquis, Juan; Vinuesa, María Angeles; Pomilio, Carlos Javier; Pavía, Patricio Roberto; Galvan, Verónica; Saravia, Flavia Eugenia
Año de publicación
2014
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
In the context of Alzheimer's disease (AD), hippocampal alterations have been well described in advanced stages of the pathology, when amyloid deposition, inflammation and glial activation occur, but less attention has been directed to studying early brain and behavioral changes. Using an animal model of AD, the transgenic PDAPP-J20 mouse at 5 months of age, when no amyloid plaques are present and low cerebral levels of amyloid peptides are detectable, we found structural, morphological, and cellular alterations in the hippocampus. Young transgenic mice showed a reduced hippocampal volume with less number of pyramidal and granular neurons, which additionally exhibited cell atrophy. The neurogenic capability in this zone, measured as DCX+ cells, was strongly diminished and associated to alterations in cell maturity. A decrease in presynaptic synaptophysin optical density was detected in mossy fibers reaching CA3 subfield but not in Golgi stained- CA1 dendritic spine density. Employing confocal microscopy and accurate stereological tools we also found a reduction in the number of GFAP+ cells, along with decreased astrocyte complexity, suggesting a potential detriment of neural support. According with untimely neuroglial alterations, young PDAPP mice failed in the novel location recognition test, that depends on hippocampal function. Moreover, multivariate statistical analysis of the behavioral outcome in the open-field test evidenced an elevated anxiety score in Tg mice compared with age-matched control mice. In line with this, the transgenic group showed a higher number of c-Fos+ nuclei in central and basolateral amygdala, a result that supports the early involvement of the emotionality factor in AD pathology. Applying an integrative approach, this work focuses on early structural, morphological and functional changes and provides new and compelling evidence of behavioral alterations that precede manifest AD.
Fil: Beauquis, Juan. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
Fil: Vinuesa, María Angeles. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
Fil: Pomilio, Carlos Javier. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
Fil: Pavía, Patricio Roberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
Fil: Galvan, Verónica. University of Texas; Estados Unidos
Fil: Saravia, Flavia Eugenia. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
Materia
Cognitive Deficit And Anxiety
Dcx
Glia
Pdapp Mouse Model of Alzheimer'S Disease
Pyramidal And Granular Neurons
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/6442
Acceder
id CONICETDig_b720da4ba60bc8cd94b9538657a4e87e
oai_identifier_str oai:ri.conicet.gov.ar:11336/6442
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Neuronal and glial alterations, increased anxiety, and cognitive impairment before hippocampal amyloid deposition in PDAPP mice, model of Alzheimer's diseaseBeauquis, JuanVinuesa, María AngelesPomilio, Carlos JavierPavía, Patricio RobertoGalvan, VerónicaSaravia, Flavia EugeniaCognitive Deficit And AnxietyDcxGliaPdapp Mouse Model of Alzheimer'S DiseasePyramidal And Granular Neuronshttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3In the context of Alzheimer's disease (AD), hippocampal alterations have been well described in advanced stages of the pathology, when amyloid deposition, inflammation and glial activation occur, but less attention has been directed to studying early brain and behavioral changes. Using an animal model of AD, the transgenic PDAPP-J20 mouse at 5 months of age, when no amyloid plaques are present and low cerebral levels of amyloid peptides are detectable, we found structural, morphological, and cellular alterations in the hippocampus. Young transgenic mice showed a reduced hippocampal volume with less number of pyramidal and granular neurons, which additionally exhibited cell atrophy. The neurogenic capability in this zone, measured as DCX+ cells, was strongly diminished and associated to alterations in cell maturity. A decrease in presynaptic synaptophysin optical density was detected in mossy fibers reaching CA3 subfield but not in Golgi stained- CA1 dendritic spine density. Employing confocal microscopy and accurate stereological tools we also found a reduction in the number of GFAP+ cells, along with decreased astrocyte complexity, suggesting a potential detriment of neural support. According with untimely neuroglial alterations, young PDAPP mice failed in the novel location recognition test, that depends on hippocampal function. Moreover, multivariate statistical analysis of the behavioral outcome in the open-field test evidenced an elevated anxiety score in Tg mice compared with age-matched control mice. In line with this, the transgenic group showed a higher number of c-Fos+ nuclei in central and basolateral amygdala, a result that supports the early involvement of the emotionality factor in AD pathology. Applying an integrative approach, this work focuses on early structural, morphological and functional changes and provides new and compelling evidence of behavioral alterations that precede manifest AD.Fil: Beauquis, Juan. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Vinuesa, María Angeles. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Pomilio, Carlos Javier. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Pavía, Patricio Roberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Galvan, Verónica. University of Texas; Estados UnidosFil: Saravia, Flavia Eugenia. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaWiley-liss, Div John Wiley & Sons Inc2014-02-14info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/6442Beauquis, Juan; Vinuesa, María Angeles; Pomilio, Carlos Javier; Pavía, Patricio Roberto; Galvan, Verónica; et al.; Neuronal and glial alterations, increased anxiety, and cognitive impairment before hippocampal amyloid deposition in PDAPP mice, model of Alzheimer's disease; Wiley-liss, Div John Wiley & Sons Inc; Hippocampus; 24; 3; 14-2-2014; 257-2691050-96311098-1063enginfo:eu-repo/semantics/altIdentifier/doi/10.1002/hipo.22219info:eu-repo/semantics/altIdentifier/pmid/24132937info:eu-repo/semantics/altIdentifier/url/http://onlinelibrary.wiley.com/doi/10.1002/hipo.22219/abstractinfo:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T09:47:41Zoai:ri.conicet.gov.ar:11336/6442instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-29 09:47:41.427CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Neuronal and glial alterations, increased anxiety, and cognitive impairment before hippocampal amyloid deposition in PDAPP mice, model of Alzheimer's disease
title Neuronal and glial alterations, increased anxiety, and cognitive impairment before hippocampal amyloid deposition in PDAPP mice, model of Alzheimer's disease
spellingShingle Neuronal and glial alterations, increased anxiety, and cognitive impairment before hippocampal amyloid deposition in PDAPP mice, model of Alzheimer's disease
Beauquis, Juan
Cognitive Deficit And Anxiety
Dcx
Glia
Pdapp Mouse Model of Alzheimer'S Disease
Pyramidal And Granular Neurons
title_short Neuronal and glial alterations, increased anxiety, and cognitive impairment before hippocampal amyloid deposition in PDAPP mice, model of Alzheimer's disease
title_full Neuronal and glial alterations, increased anxiety, and cognitive impairment before hippocampal amyloid deposition in PDAPP mice, model of Alzheimer's disease
title_fullStr Neuronal and glial alterations, increased anxiety, and cognitive impairment before hippocampal amyloid deposition in PDAPP mice, model of Alzheimer's disease
title_full_unstemmed Neuronal and glial alterations, increased anxiety, and cognitive impairment before hippocampal amyloid deposition in PDAPP mice, model of Alzheimer's disease
title_sort Neuronal and glial alterations, increased anxiety, and cognitive impairment before hippocampal amyloid deposition in PDAPP mice, model of Alzheimer's disease
dc.creator.none.fl_str_mv Beauquis, Juan
Vinuesa, María Angeles
Pomilio, Carlos Javier
Pavía, Patricio Roberto
Galvan, Verónica
Saravia, Flavia Eugenia
author Beauquis, Juan
author_facet Beauquis, Juan
Vinuesa, María Angeles
Pomilio, Carlos Javier
Pavía, Patricio Roberto
Galvan, Verónica
Saravia, Flavia Eugenia
author_role author
author2 Vinuesa, María Angeles
Pomilio, Carlos Javier
Pavía, Patricio Roberto
Galvan, Verónica
Saravia, Flavia Eugenia
author2_role author
author
author
author
author
dc.subject.none.fl_str_mv Cognitive Deficit And Anxiety
Dcx
Glia
Pdapp Mouse Model of Alzheimer'S Disease
Pyramidal And Granular Neurons
topic Cognitive Deficit And Anxiety
Dcx
Glia
Pdapp Mouse Model of Alzheimer'S Disease
Pyramidal And Granular Neurons
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv In the context of Alzheimer's disease (AD), hippocampal alterations have been well described in advanced stages of the pathology, when amyloid deposition, inflammation and glial activation occur, but less attention has been directed to studying early brain and behavioral changes. Using an animal model of AD, the transgenic PDAPP-J20 mouse at 5 months of age, when no amyloid plaques are present and low cerebral levels of amyloid peptides are detectable, we found structural, morphological, and cellular alterations in the hippocampus. Young transgenic mice showed a reduced hippocampal volume with less number of pyramidal and granular neurons, which additionally exhibited cell atrophy. The neurogenic capability in this zone, measured as DCX+ cells, was strongly diminished and associated to alterations in cell maturity. A decrease in presynaptic synaptophysin optical density was detected in mossy fibers reaching CA3 subfield but not in Golgi stained- CA1 dendritic spine density. Employing confocal microscopy and accurate stereological tools we also found a reduction in the number of GFAP+ cells, along with decreased astrocyte complexity, suggesting a potential detriment of neural support. According with untimely neuroglial alterations, young PDAPP mice failed in the novel location recognition test, that depends on hippocampal function. Moreover, multivariate statistical analysis of the behavioral outcome in the open-field test evidenced an elevated anxiety score in Tg mice compared with age-matched control mice. In line with this, the transgenic group showed a higher number of c-Fos+ nuclei in central and basolateral amygdala, a result that supports the early involvement of the emotionality factor in AD pathology. Applying an integrative approach, this work focuses on early structural, morphological and functional changes and provides new and compelling evidence of behavioral alterations that precede manifest AD.
Fil: Beauquis, Juan. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
Fil: Vinuesa, María Angeles. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
Fil: Pomilio, Carlos Javier. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
Fil: Pavía, Patricio Roberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
Fil: Galvan, Verónica. University of Texas; Estados Unidos
Fil: Saravia, Flavia Eugenia. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
description In the context of Alzheimer's disease (AD), hippocampal alterations have been well described in advanced stages of the pathology, when amyloid deposition, inflammation and glial activation occur, but less attention has been directed to studying early brain and behavioral changes. Using an animal model of AD, the transgenic PDAPP-J20 mouse at 5 months of age, when no amyloid plaques are present and low cerebral levels of amyloid peptides are detectable, we found structural, morphological, and cellular alterations in the hippocampus. Young transgenic mice showed a reduced hippocampal volume with less number of pyramidal and granular neurons, which additionally exhibited cell atrophy. The neurogenic capability in this zone, measured as DCX+ cells, was strongly diminished and associated to alterations in cell maturity. A decrease in presynaptic synaptophysin optical density was detected in mossy fibers reaching CA3 subfield but not in Golgi stained- CA1 dendritic spine density. Employing confocal microscopy and accurate stereological tools we also found a reduction in the number of GFAP+ cells, along with decreased astrocyte complexity, suggesting a potential detriment of neural support. According with untimely neuroglial alterations, young PDAPP mice failed in the novel location recognition test, that depends on hippocampal function. Moreover, multivariate statistical analysis of the behavioral outcome in the open-field test evidenced an elevated anxiety score in Tg mice compared with age-matched control mice. In line with this, the transgenic group showed a higher number of c-Fos+ nuclei in central and basolateral amygdala, a result that supports the early involvement of the emotionality factor in AD pathology. Applying an integrative approach, this work focuses on early structural, morphological and functional changes and provides new and compelling evidence of behavioral alterations that precede manifest AD.
publishDate 2014
dc.date.none.fl_str_mv 2014-02-14
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/6442
Beauquis, Juan; Vinuesa, María Angeles; Pomilio, Carlos Javier; Pavía, Patricio Roberto; Galvan, Verónica; et al.; Neuronal and glial alterations, increased anxiety, and cognitive impairment before hippocampal amyloid deposition in PDAPP mice, model of Alzheimer's disease; Wiley-liss, Div John Wiley & Sons Inc; Hippocampus; 24; 3; 14-2-2014; 257-269
1050-9631
1098-1063
url http://hdl.handle.net/11336/6442
identifier_str_mv Beauquis, Juan; Vinuesa, María Angeles; Pomilio, Carlos Javier; Pavía, Patricio Roberto; Galvan, Verónica; et al.; Neuronal and glial alterations, increased anxiety, and cognitive impairment before hippocampal amyloid deposition in PDAPP mice, model of Alzheimer's disease; Wiley-liss, Div John Wiley & Sons Inc; Hippocampus; 24; 3; 14-2-2014; 257-269
1050-9631
1098-1063
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1002/hipo.22219
info:eu-repo/semantics/altIdentifier/pmid/24132937
info:eu-repo/semantics/altIdentifier/url/http://onlinelibrary.wiley.com/doi/10.1002/hipo.22219/abstract
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
application/pdf
dc.publisher.none.fl_str_mv Wiley-liss, Div John Wiley & Sons Inc
publisher.none.fl_str_mv Wiley-liss, Div John Wiley & Sons Inc
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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score 13.070432

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