Estradiol activates PI3K/Akt/GSK3 pathway under chronic neurodegenerative conditions triggered by perinatal asphyxia

Autores
Saraceno, Gustavo Ezequiel; Bellini, Maria Jose; Garcia Segura, Luis Miguel; Capani, Francisco
Año de publicación
2018
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Perinatal asphyxia (PA) remains as one of the most important causes of short-term mortality, psychiatric and neurological disorders in children, without an effective treatment. In previous studies we have observed that the expression of different neurodegenerative markers increases in CA1 hippocampal area of 4-months-old male rats born by cesarean section and exposed for 19 min to PA. We have also shown that a late treatment with 17β estradiol (daily dose of 250 μg/kg for 3 days) was able to revert the brain alterations observed in those animals. Based on these previous results, the main aim of the present study was to explore the mechanism by which the estrogenic treatment is involved in the reversion of the chronic neurodegenerative conditions induced by PA. We demonstrated that estradiol treatment of adult PA exposed animals induced an increase in estrogen receptor (ER) a and insulin-like growth factor receptor (IGF-1R) protein levels, an activation of the phosphatidylinositol 3-kinase/Akt/glycogen synthase kinase 3 beta/β-catenin signaling pathway and an increase in Bcl-2/Bax ratio in the hippocampus in comparison to PA exposed animals treated with vehicle. Taking together, our data suggest that the interaction between ERa and IGF-IR, with the subsequent downstream activation, underlies the beneficial effects of estradiol observed in late treatment of PA.
Fil: Saraceno, Gustavo Ezequiel. Universite de Bordeaux; Francia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Cardiológicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Cardiológicas; Argentina
Fil: Bellini, Maria Jose. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Bioquímicas de La Plata "Prof. Dr. Rodolfo R. Brenner". Universidad Nacional de la Plata. Facultad de Ciencias Médicas. Instituto de Investigaciones Bioquímicas de La Plata "Prof. Dr. Rodolfo R. Brenner"; Argentina
Fil: Garcia Segura, Luis Miguel. Consejo Superior de Investigaciones Científicas; España. Instituto de Salud Carlos III; España
Fil: Capani, Francisco. Universidad Autónoma de Chile; Chile. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Cardiológicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Cardiológicas; Argentina
Materia
HIPPOCAMPUS
NEURONAL SURVIVAL
NEUROPROTECTION
SIGNALING PATHWAY
WESTERN BLOT
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/99309
Acceder
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network_name_str CONICET Digital (CONICET)
spelling Estradiol activates PI3K/Akt/GSK3 pathway under chronic neurodegenerative conditions triggered by perinatal asphyxiaSaraceno, Gustavo EzequielBellini, Maria JoseGarcia Segura, Luis MiguelCapani, FranciscoHIPPOCAMPUSNEURONAL SURVIVALNEUROPROTECTIONSIGNALING PATHWAYWESTERN BLOThttps://purl.org/becyt/ford/3.5https://purl.org/becyt/ford/3Perinatal asphyxia (PA) remains as one of the most important causes of short-term mortality, psychiatric and neurological disorders in children, without an effective treatment. In previous studies we have observed that the expression of different neurodegenerative markers increases in CA1 hippocampal area of 4-months-old male rats born by cesarean section and exposed for 19 min to PA. We have also shown that a late treatment with 17β estradiol (daily dose of 250 μg/kg for 3 days) was able to revert the brain alterations observed in those animals. Based on these previous results, the main aim of the present study was to explore the mechanism by which the estrogenic treatment is involved in the reversion of the chronic neurodegenerative conditions induced by PA. We demonstrated that estradiol treatment of adult PA exposed animals induced an increase in estrogen receptor (ER) a and insulin-like growth factor receptor (IGF-1R) protein levels, an activation of the phosphatidylinositol 3-kinase/Akt/glycogen synthase kinase 3 beta/β-catenin signaling pathway and an increase in Bcl-2/Bax ratio in the hippocampus in comparison to PA exposed animals treated with vehicle. Taking together, our data suggest that the interaction between ERa and IGF-IR, with the subsequent downstream activation, underlies the beneficial effects of estradiol observed in late treatment of PA.Fil: Saraceno, Gustavo Ezequiel. Universite de Bordeaux; Francia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Cardiológicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Cardiológicas; ArgentinaFil: Bellini, Maria Jose. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Bioquímicas de La Plata "Prof. Dr. Rodolfo R. Brenner". Universidad Nacional de la Plata. Facultad de Ciencias Médicas. Instituto de Investigaciones Bioquímicas de La Plata "Prof. Dr. Rodolfo R. Brenner"; ArgentinaFil: Garcia Segura, Luis Miguel. Consejo Superior de Investigaciones Científicas; España. Instituto de Salud Carlos III; EspañaFil: Capani, Francisco. Universidad Autónoma de Chile; Chile. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Cardiológicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Cardiológicas; ArgentinaFrontiers Media S.A.2018-04info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/99309Saraceno, Gustavo Ezequiel; Bellini, Maria Jose; Garcia Segura, Luis Miguel; Capani, Francisco; Estradiol activates PI3K/Akt/GSK3 pathway under chronic neurodegenerative conditions triggered by perinatal asphyxia; Frontiers Media S.A.; Frontiers in Pharmacology; 9; APR; 4-2018; 1-101663-9812CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://www.frontiersin.org/articles/10.3389/fphar.2018.00335/fullinfo:eu-repo/semantics/altIdentifier/doi/10.3389/fphar.2018.00335info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-10-22T11:00:36Zoai:ri.conicet.gov.ar:11336/99309instacron: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:34982025-10-22 11:00:36.717CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Estradiol activates PI3K/Akt/GSK3 pathway under chronic neurodegenerative conditions triggered by perinatal asphyxia
title Estradiol activates PI3K/Akt/GSK3 pathway under chronic neurodegenerative conditions triggered by perinatal asphyxia
spellingShingle Estradiol activates PI3K/Akt/GSK3 pathway under chronic neurodegenerative conditions triggered by perinatal asphyxia
Saraceno, Gustavo Ezequiel
HIPPOCAMPUS
NEURONAL SURVIVAL
NEUROPROTECTION
SIGNALING PATHWAY
WESTERN BLOT
title_short Estradiol activates PI3K/Akt/GSK3 pathway under chronic neurodegenerative conditions triggered by perinatal asphyxia
title_full Estradiol activates PI3K/Akt/GSK3 pathway under chronic neurodegenerative conditions triggered by perinatal asphyxia
title_fullStr Estradiol activates PI3K/Akt/GSK3 pathway under chronic neurodegenerative conditions triggered by perinatal asphyxia
title_full_unstemmed Estradiol activates PI3K/Akt/GSK3 pathway under chronic neurodegenerative conditions triggered by perinatal asphyxia
title_sort Estradiol activates PI3K/Akt/GSK3 pathway under chronic neurodegenerative conditions triggered by perinatal asphyxia
dc.creator.none.fl_str_mv Saraceno, Gustavo Ezequiel
Bellini, Maria Jose
Garcia Segura, Luis Miguel
Capani, Francisco
author Saraceno, Gustavo Ezequiel
author_facet Saraceno, Gustavo Ezequiel
Bellini, Maria Jose
Garcia Segura, Luis Miguel
Capani, Francisco
author_role author
author2 Bellini, Maria Jose
Garcia Segura, Luis Miguel
Capani, Francisco
author2_role author
author
author
dc.subject.none.fl_str_mv HIPPOCAMPUS
NEURONAL SURVIVAL
NEUROPROTECTION
SIGNALING PATHWAY
WESTERN BLOT
topic HIPPOCAMPUS
NEURONAL SURVIVAL
NEUROPROTECTION
SIGNALING PATHWAY
WESTERN BLOT
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.5
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Perinatal asphyxia (PA) remains as one of the most important causes of short-term mortality, psychiatric and neurological disorders in children, without an effective treatment. In previous studies we have observed that the expression of different neurodegenerative markers increases in CA1 hippocampal area of 4-months-old male rats born by cesarean section and exposed for 19 min to PA. We have also shown that a late treatment with 17β estradiol (daily dose of 250 μg/kg for 3 days) was able to revert the brain alterations observed in those animals. Based on these previous results, the main aim of the present study was to explore the mechanism by which the estrogenic treatment is involved in the reversion of the chronic neurodegenerative conditions induced by PA. We demonstrated that estradiol treatment of adult PA exposed animals induced an increase in estrogen receptor (ER) a and insulin-like growth factor receptor (IGF-1R) protein levels, an activation of the phosphatidylinositol 3-kinase/Akt/glycogen synthase kinase 3 beta/β-catenin signaling pathway and an increase in Bcl-2/Bax ratio in the hippocampus in comparison to PA exposed animals treated with vehicle. Taking together, our data suggest that the interaction between ERa and IGF-IR, with the subsequent downstream activation, underlies the beneficial effects of estradiol observed in late treatment of PA.
Fil: Saraceno, Gustavo Ezequiel. Universite de Bordeaux; Francia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Cardiológicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Cardiológicas; Argentina
Fil: Bellini, Maria Jose. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Bioquímicas de La Plata "Prof. Dr. Rodolfo R. Brenner". Universidad Nacional de la Plata. Facultad de Ciencias Médicas. Instituto de Investigaciones Bioquímicas de La Plata "Prof. Dr. Rodolfo R. Brenner"; Argentina
Fil: Garcia Segura, Luis Miguel. Consejo Superior de Investigaciones Científicas; España. Instituto de Salud Carlos III; España
Fil: Capani, Francisco. Universidad Autónoma de Chile; Chile. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Cardiológicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Cardiológicas; Argentina
description Perinatal asphyxia (PA) remains as one of the most important causes of short-term mortality, psychiatric and neurological disorders in children, without an effective treatment. In previous studies we have observed that the expression of different neurodegenerative markers increases in CA1 hippocampal area of 4-months-old male rats born by cesarean section and exposed for 19 min to PA. We have also shown that a late treatment with 17β estradiol (daily dose of 250 μg/kg for 3 days) was able to revert the brain alterations observed in those animals. Based on these previous results, the main aim of the present study was to explore the mechanism by which the estrogenic treatment is involved in the reversion of the chronic neurodegenerative conditions induced by PA. We demonstrated that estradiol treatment of adult PA exposed animals induced an increase in estrogen receptor (ER) a and insulin-like growth factor receptor (IGF-1R) protein levels, an activation of the phosphatidylinositol 3-kinase/Akt/glycogen synthase kinase 3 beta/β-catenin signaling pathway and an increase in Bcl-2/Bax ratio in the hippocampus in comparison to PA exposed animals treated with vehicle. Taking together, our data suggest that the interaction between ERa and IGF-IR, with the subsequent downstream activation, underlies the beneficial effects of estradiol observed in late treatment of PA.
publishDate 2018
dc.date.none.fl_str_mv 2018-04
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/11336/99309
Saraceno, Gustavo Ezequiel; Bellini, Maria Jose; Garcia Segura, Luis Miguel; Capani, Francisco; Estradiol activates PI3K/Akt/GSK3 pathway under chronic neurodegenerative conditions triggered by perinatal asphyxia; Frontiers Media S.A.; Frontiers in Pharmacology; 9; APR; 4-2018; 1-10
1663-9812
CONICET Digital
CONICET
url http://hdl.handle.net/11336/99309
identifier_str_mv Saraceno, Gustavo Ezequiel; Bellini, Maria Jose; Garcia Segura, Luis Miguel; Capani, Francisco; Estradiol activates PI3K/Akt/GSK3 pathway under chronic neurodegenerative conditions triggered by perinatal asphyxia; Frontiers Media S.A.; Frontiers in Pharmacology; 9; APR; 4-2018; 1-10
1663-9812
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/https://www.frontiersin.org/articles/10.3389/fphar.2018.00335/full
info:eu-repo/semantics/altIdentifier/doi/10.3389/fphar.2018.00335
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
application/pdf
application/pdf
dc.publisher.none.fl_str_mv Frontiers Media S.A.
publisher.none.fl_str_mv Frontiers Media S.A.
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 12.982451

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