Deletion of Gadd45a Expression in Mice Leads to Cognitive and Synaptic Impairment Associated with Alzheimer's Disease Hallmarks

Gadd45 genes have been implicated in survival mechanisms, including apoptosis, autophagy, cell cycle arrest, and DNA repair, which are processes related to aging and life span. Here, we analyzed if the deletion of Gadd45a activates pathways involved in neurodegenerative disorders such as Alzheimer&#...

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Autores: Griñán-Ferré C, Jarne-Ferrer J, Bellver-Sanchis A, Ribalta-Vilella M, Barroso E, Salvador JM, Jurado-Aguilar J, Palomer X, Vázquez-Carrera M, Pallàs M
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2024
País:España
Institución:Fundació Sant Joan de Déu
Repositorio:r-FSJD. Repositorio Institucional de Producción Científica de la Fundació Sant Joan de Déu
OAI Identifier:oai:fsjd.fundanetsuite.com:p25880
Acceso en línea:https://fsjd.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=25880
Access Level:acceso abierto
Palabra clave:cognitive impairment
Alzheimer's disease
Tau pathology
neuroinflammation
Gadd45a
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spelling Deletion of Gadd45a Expression in Mice Leads to Cognitive and Synaptic Impairment Associated with Alzheimer's Disease HallmarksGriñán-Ferré CJarne-Ferrer JBellver-Sanchis ARibalta-Vilella MBarroso ESalvador JMJurado-Aguilar JPalomer XVázquez-Carrera MPallàs Mcognitive impairmentAlzheimer's diseaseTau pathologyneuroinflammationGadd45aGadd45 genes have been implicated in survival mechanisms, including apoptosis, autophagy, cell cycle arrest, and DNA repair, which are processes related to aging and life span. Here, we analyzed if the deletion of Gadd45a activates pathways involved in neurodegenerative disorders such as Alzheimer's Disease (AD). This study used wild-type (WT) and Gadd45a knockout (Gadd45a(-/-)) mice to evaluate AD progression. Behavioral tests showed that Gadd45a(-/-) mice presented lower working and spatial memory, pointing out an apparent cognitive impairment compared with WT animals, accompanied by an increase in Tau hyperphosphorylation and the levels of kinases involved in its phosphorylation in the hippocampus. Moreover, Gadd45a(-/-) animals significantly increased the brain's pro-inflammatory cytokines and modified autophagy markers. Notably, neurotrophins and the dendritic spine length of the neurons were reduced in Gadd45a(-/-) mice, which could contribute to the cognitive alterations observed in these animals. Overall, these findings demonstrate that the lack of the Gadd45a gene activates several pathways that exacerbate AD pathology, suggesting that promoting this protein's expression or function might be a promising therapeutic strategy to slow down AD progression.MDPI2024info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttps://fsjd.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=25880INTERNATIONAL JOURNAL OF MOLECULAR SCIENCESISSN: 16616596ISSNe: 14220067reponame:r-FSJD. Repositorio Institucional de Producción Científica de la Fundació Sant Joan de Déuinstname:Fundació Sant Joan de DéuInglésinfo:eu-repo/semantics/openAccessoai:fsjd.fundanetsuite.com:p258802026-05-27T12:37:41Z
dc.title.none.fl_str_mv Deletion of Gadd45a Expression in Mice Leads to Cognitive and Synaptic Impairment Associated with Alzheimer's Disease Hallmarks
title Deletion of Gadd45a Expression in Mice Leads to Cognitive and Synaptic Impairment Associated with Alzheimer's Disease Hallmarks
spellingShingle Deletion of Gadd45a Expression in Mice Leads to Cognitive and Synaptic Impairment Associated with Alzheimer's Disease Hallmarks
Griñán-Ferré C
cognitive impairment
Alzheimer's disease
Tau pathology
neuroinflammation
Gadd45a
title_short Deletion of Gadd45a Expression in Mice Leads to Cognitive and Synaptic Impairment Associated with Alzheimer's Disease Hallmarks
title_full Deletion of Gadd45a Expression in Mice Leads to Cognitive and Synaptic Impairment Associated with Alzheimer's Disease Hallmarks
title_fullStr Deletion of Gadd45a Expression in Mice Leads to Cognitive and Synaptic Impairment Associated with Alzheimer's Disease Hallmarks
title_full_unstemmed Deletion of Gadd45a Expression in Mice Leads to Cognitive and Synaptic Impairment Associated with Alzheimer's Disease Hallmarks
title_sort Deletion of Gadd45a Expression in Mice Leads to Cognitive and Synaptic Impairment Associated with Alzheimer's Disease Hallmarks
dc.creator.none.fl_str_mv Griñán-Ferré C
Jarne-Ferrer J
Bellver-Sanchis A
Ribalta-Vilella M
Barroso E
Salvador JM
Jurado-Aguilar J
Palomer X
Vázquez-Carrera M
Pallàs M
author Griñán-Ferré C
author_facet Griñán-Ferré C
Jarne-Ferrer J
Bellver-Sanchis A
Ribalta-Vilella M
Barroso E
Salvador JM
Jurado-Aguilar J
Palomer X
Vázquez-Carrera M
Pallàs M
author_role author
author2 Jarne-Ferrer J
Bellver-Sanchis A
Ribalta-Vilella M
Barroso E
Salvador JM
Jurado-Aguilar J
Palomer X
Vázquez-Carrera M
Pallàs M
author2_role author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv cognitive impairment
Alzheimer's disease
Tau pathology
neuroinflammation
Gadd45a
topic cognitive impairment
Alzheimer's disease
Tau pathology
neuroinflammation
Gadd45a
description Gadd45 genes have been implicated in survival mechanisms, including apoptosis, autophagy, cell cycle arrest, and DNA repair, which are processes related to aging and life span. Here, we analyzed if the deletion of Gadd45a activates pathways involved in neurodegenerative disorders such as Alzheimer's Disease (AD). This study used wild-type (WT) and Gadd45a knockout (Gadd45a(-/-)) mice to evaluate AD progression. Behavioral tests showed that Gadd45a(-/-) mice presented lower working and spatial memory, pointing out an apparent cognitive impairment compared with WT animals, accompanied by an increase in Tau hyperphosphorylation and the levels of kinases involved in its phosphorylation in the hippocampus. Moreover, Gadd45a(-/-) animals significantly increased the brain's pro-inflammatory cytokines and modified autophagy markers. Notably, neurotrophins and the dendritic spine length of the neurons were reduced in Gadd45a(-/-) mice, which could contribute to the cognitive alterations observed in these animals. Overall, these findings demonstrate that the lack of the Gadd45a gene activates several pathways that exacerbate AD pathology, suggesting that promoting this protein's expression or function might be a promising therapeutic strategy to slow down AD progression.
publishDate 2024
dc.date.none.fl_str_mv 2024
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://fsjd.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=25880
url https://fsjd.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=25880
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv MDPI
publisher.none.fl_str_mv MDPI
dc.source.none.fl_str_mv INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
ISSN: 16616596
ISSNe: 14220067
reponame:r-FSJD. Repositorio Institucional de Producción Científica de la Fundació Sant Joan de Déu
instname:Fundació Sant Joan de Déu
instname_str Fundació Sant Joan de Déu
reponame_str r-FSJD. Repositorio Institucional de Producción Científica de la Fundació Sant Joan de Déu
collection r-FSJD. Repositorio Institucional de Producción Científica de la Fundació Sant Joan de Déu
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,81155

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