Different susceptibility to neurodegeneration of dorsal and ventral hippocampal dentate gyrus: A study with transgenic mice overexpressing GSK3β

Dorsal hippocampal regions are involved in memory and learning processes, while ventral areas are related to emotional and anxiety processes. Hippocampal dependent memory and behaviour alterations do not always come out in neurodegenerative diseases at the same time. In this study we have tested the...

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Authors: Fuster-Matanzo, Almudena, Lloréns-Martín, María V., Gómez De Barreda, Elena, Ávila, Jesús, Hernández Pérez, Félix
Format: article
Publication Date:2011
Country:España
Institution:Universidad Autónoma de Madrid
Repository:Biblos-e Archivo. Repositorio Institucional de la UAM
Language:English
OAI Identifier:oai:repositorio.uam.es:10486/665764
Online Access:http://hdl.handle.net/10486/665764
https://dx.doi.org/10.1371/journal.pone.0027262
Access Level:Open access
Keyword:Behavior, Animal
Darkness
Dentate Gyrus
Phosphorylation
Glycogen Synthase Kinase 3
Biología y Biomedicina / Biología
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spelling Different susceptibility to neurodegeneration of dorsal and ventral hippocampal dentate gyrus: A study with transgenic mice overexpressing GSK3βFuster-Matanzo, AlmudenaLloréns-Martín, María V.Gómez De Barreda, ElenaÁvila, JesúsHernández Pérez, FélixBehavior, AnimalDarknessDentate GyrusPhosphorylationGlycogen Synthase Kinase 3Biología y Biomedicina / BiologíaDorsal hippocampal regions are involved in memory and learning processes, while ventral areas are related to emotional and anxiety processes. Hippocampal dependent memory and behaviour alterations do not always come out in neurodegenerative diseases at the same time. In this study we have tested the hypothesis that dorsal and ventral dentate gyrus (DG) regions respond in a different manner to increased glycogen synthase kinase-3β (GSK3β) levels in GSK3β transgenic mice, a genetic model of neurodegeneration. Reactive astrocytosis indicate tissue stress in dorsal DG, while ventral area does not show that marker. These changes occurred with a significant reduction of total cell number and with a significantly higher level of cell death in dorsal area than in ventral one as measured by fractin-positive cells. Biochemistry analysis showed higher levels of phosphorylated GSK3β in those residues that inactivate the enzyme in hippocampal ventral areas compared with dorsal area suggesting that the observed susceptibility is in part due to different GSK3 regulation. Previous studies carried out with this animal model had demonstrated impairment in Morris Water Maze and Object recognition tests point out to dorsal hippocampal atrophy. Here, we show that two tests used to evaluate emotional status, the light-dark box and the novelty suppressed feeding test, suggest that GSK3β mice do not show any anxiety-related disorder. Thus, our results demonstrate that in vivo overexpression of GSK3β results in dorsal but not ventral hippocampal DG neurodegeneration and suggest that both areas do not behave in a similar manner in neurodegenerative processesThis work was supported by grants from the Spanish Comisión Interministerial de Ciencia y Tecnología (CICYT; SAF2010-15525, SAF 2006-02424), the Comunidad de Madrid (NEURODEGMODELS-CM, SAL/0202/2006), Fundación Centro de Investigaciones de Enfermedades Neurológicas (Fundación CIEN, PI 008- 09), the Centro de Investigación Biomédica en Red on Neurodegeneration (CIBER) and by institutional grants from Fundación Botín and Fundación Ramón ArecesPublic Library of ScienceDepartamento de Biología MolecularFacultad de Ciencias20112011-11-03research articlehttp://purl.org/coar/resource_type/c_2df8fbb1VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10486/665764https://dx.doi.org/10.1371/journal.pone.0027262reponame:Biblos-e Archivo. Repositorio Institucional de la UAMinstname:Universidad Autónoma de MadridInglésengopen accesshttp://purl.org/coar/access_right/c_abf2info:eu-repo/semantics/openAccessoai:repositorio.uam.es:10486/6657642026-06-23T12:46:27Z
dc.title.none.fl_str_mv Different susceptibility to neurodegeneration of dorsal and ventral hippocampal dentate gyrus: A study with transgenic mice overexpressing GSK3β
title Different susceptibility to neurodegeneration of dorsal and ventral hippocampal dentate gyrus: A study with transgenic mice overexpressing GSK3β
spellingShingle Different susceptibility to neurodegeneration of dorsal and ventral hippocampal dentate gyrus: A study with transgenic mice overexpressing GSK3β
Fuster-Matanzo, Almudena
Behavior, Animal
Darkness
Dentate Gyrus
Phosphorylation
Glycogen Synthase Kinase 3
Biología y Biomedicina / Biología
title_short Different susceptibility to neurodegeneration of dorsal and ventral hippocampal dentate gyrus: A study with transgenic mice overexpressing GSK3β
title_full Different susceptibility to neurodegeneration of dorsal and ventral hippocampal dentate gyrus: A study with transgenic mice overexpressing GSK3β
title_fullStr Different susceptibility to neurodegeneration of dorsal and ventral hippocampal dentate gyrus: A study with transgenic mice overexpressing GSK3β
title_full_unstemmed Different susceptibility to neurodegeneration of dorsal and ventral hippocampal dentate gyrus: A study with transgenic mice overexpressing GSK3β
title_sort Different susceptibility to neurodegeneration of dorsal and ventral hippocampal dentate gyrus: A study with transgenic mice overexpressing GSK3β
dc.creator.none.fl_str_mv Fuster-Matanzo, Almudena
Lloréns-Martín, María V.
Gómez De Barreda, Elena
Ávila, Jesús
Hernández Pérez, Félix
author Fuster-Matanzo, Almudena
author_facet Fuster-Matanzo, Almudena
Lloréns-Martín, María V.
Gómez De Barreda, Elena
Ávila, Jesús
Hernández Pérez, Félix
author_role author
author2 Lloréns-Martín, María V.
Gómez De Barreda, Elena
Ávila, Jesús
Hernández Pérez, Félix
author2_role author
author
author
author
dc.contributor.none.fl_str_mv Departamento de Biología Molecular
Facultad de Ciencias
dc.subject.none.fl_str_mv Behavior, Animal
Darkness
Dentate Gyrus
Phosphorylation
Glycogen Synthase Kinase 3
Biología y Biomedicina / Biología
topic Behavior, Animal
Darkness
Dentate Gyrus
Phosphorylation
Glycogen Synthase Kinase 3
Biología y Biomedicina / Biología
description Dorsal hippocampal regions are involved in memory and learning processes, while ventral areas are related to emotional and anxiety processes. Hippocampal dependent memory and behaviour alterations do not always come out in neurodegenerative diseases at the same time. In this study we have tested the hypothesis that dorsal and ventral dentate gyrus (DG) regions respond in a different manner to increased glycogen synthase kinase-3β (GSK3β) levels in GSK3β transgenic mice, a genetic model of neurodegeneration. Reactive astrocytosis indicate tissue stress in dorsal DG, while ventral area does not show that marker. These changes occurred with a significant reduction of total cell number and with a significantly higher level of cell death in dorsal area than in ventral one as measured by fractin-positive cells. Biochemistry analysis showed higher levels of phosphorylated GSK3β in those residues that inactivate the enzyme in hippocampal ventral areas compared with dorsal area suggesting that the observed susceptibility is in part due to different GSK3 regulation. Previous studies carried out with this animal model had demonstrated impairment in Morris Water Maze and Object recognition tests point out to dorsal hippocampal atrophy. Here, we show that two tests used to evaluate emotional status, the light-dark box and the novelty suppressed feeding test, suggest that GSK3β mice do not show any anxiety-related disorder. Thus, our results demonstrate that in vivo overexpression of GSK3β results in dorsal but not ventral hippocampal DG neurodegeneration and suggest that both areas do not behave in a similar manner in neurodegenerative processes
publishDate 2011
dc.date.none.fl_str_mv 2011
2011-11-03
dc.type.none.fl_str_mv research article
http://purl.org/coar/resource_type/c_2df8fbb1
VoR
http://purl.org/coar/version/c_970fb48d4fbd8a85
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv http://hdl.handle.net/10486/665764
https://dx.doi.org/10.1371/journal.pone.0027262
url http://hdl.handle.net/10486/665764
https://dx.doi.org/10.1371/journal.pone.0027262
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
dc.rights.openaire.fl_str_mv info:eu-repo/semantics/openAccess
rights_invalid_str_mv open access
http://purl.org/coar/access_right/c_abf2
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Public Library of Science
publisher.none.fl_str_mv Public Library of Science
dc.source.none.fl_str_mv reponame:Biblos-e Archivo. Repositorio Institucional de la UAM
instname:Universidad Autónoma de Madrid
instname_str Universidad Autónoma de Madrid
reponame_str Biblos-e Archivo. Repositorio Institucional de la UAM
collection Biblos-e Archivo. Repositorio Institucional de la UAM
repository.name.fl_str_mv
repository.mail.fl_str_mv
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