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

Autores
Saraceno, Gustavo Ezequiel; Bellini, María José; García 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.
Instituto de Investigaciones Bioquímicas de La Plata
Materia
Ciencias Médicas
Hippocampus
Neuronal survival
Neuroprotection
Signaling pathway
Western blot
Nivel de accesibilidad
acceso abierto
Condiciones de uso
http://creativecommons.org/licenses/by-nc-sa/4.0/
Repositorio
SEDICI (UNLP)
Institución
Universidad Nacional de La Plata
OAI Identificador
oai:sedici.unlp.edu.ar:10915/104737
Acceder
id SEDICI_5e2ebcb0c11078bbd3596fb25d221071
oai_identifier_str oai:sedici.unlp.edu.ar:10915/104737
network_acronym_str SEDICI
repository_id_str 1329
network_name_str SEDICI (UNLP)
spelling Estradiol activates PI3K/Akt/GSK3 pathway under chronic neurodegenerative conditions triggered by perinatal asphyxiaSaraceno, Gustavo EzequielBellini, María JoséGarcía Segura, Luis MiguelCapani, FranciscoCiencias MédicasHippocampusNeuronal survivalNeuroprotectionSignaling pathwayWestern blotPerinatal 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.Instituto de Investigaciones Bioquímicas de La Plata2018-04info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionArticulohttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdf1-10http://sedici.unlp.edu.ar/handle/10915/104737enginfo:eu-repo/semantics/altIdentifier/url/http://hdl.handle.net/11336/99309info:eu-repo/semantics/altIdentifier/issn/1663-9812info:eu-repo/semantics/altIdentifier/doi/10.3389/fphar.2018.00335info:eu-repo/semantics/altIdentifier/hdl/11336/99309info:eu-repo/semantics/openAccesshttp://creativecommons.org/licenses/by-nc-sa/4.0/Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0)reponame:SEDICI (UNLP)instname:Universidad Nacional de La Platainstacron:UNLP2025-10-22T17:03:40Zoai:sedici.unlp.edu.ar:10915/104737Institucionalhttp://sedici.unlp.edu.ar/Universidad públicaNo correspondehttp://sedici.unlp.edu.ar/oai/snrdalira@sedici.unlp.edu.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:13292025-10-22 17:03:41.054SEDICI (UNLP) - Universidad Nacional de La Platafalse
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
Ciencias Médicas
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, María José
García Segura, Luis Miguel
Capani, Francisco
author Saraceno, Gustavo Ezequiel
author_facet Saraceno, Gustavo Ezequiel
Bellini, María José
García Segura, Luis Miguel
Capani, Francisco
author_role author
author2 Bellini, María José
García Segura, Luis Miguel
Capani, Francisco
author2_role author
author
author
dc.subject.none.fl_str_mv Ciencias Médicas
Hippocampus
Neuronal survival
Neuroprotection
Signaling pathway
Western blot
topic Ciencias Médicas
Hippocampus
Neuronal survival
Neuroprotection
Signaling pathway
Western blot
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.
Instituto de Investigaciones Bioquímicas de La Plata
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
Articulo
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://sedici.unlp.edu.ar/handle/10915/104737
url http://sedici.unlp.edu.ar/handle/10915/104737
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/http://hdl.handle.net/11336/99309
info:eu-repo/semantics/altIdentifier/issn/1663-9812
info:eu-repo/semantics/altIdentifier/doi/10.3389/fphar.2018.00335
info:eu-repo/semantics/altIdentifier/hdl/11336/99309
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
http://creativecommons.org/licenses/by-nc-sa/4.0/
Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0)
eu_rights_str_mv openAccess
rights_invalid_str_mv http://creativecommons.org/licenses/by-nc-sa/4.0/
Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0)
dc.format.none.fl_str_mv application/pdf
1-10
dc.source.none.fl_str_mv reponame:SEDICI (UNLP)
instname:Universidad Nacional de La Plata
instacron:UNLP
reponame_str SEDICI (UNLP)
collection SEDICI (UNLP)
instname_str Universidad Nacional de La Plata
instacron_str UNLP
institution UNLP
repository.name.fl_str_mv SEDICI (UNLP) - Universidad Nacional de La Plata
repository.mail.fl_str_mv alira@sedici.unlp.edu.ar
_version_ 1846783304648359936
score 12.982451

Publicaciones similares