Estradiol-mediated axogenesis of hypothalamic neurons requires ERK1/2 and ryanodine receptors-dependent intracellular Ca2+ rise in male rats

Autores
Cabrera Zapata, Lucas Ezequiel; Bollo, Mariana Ines; Cambiasso, Maria Julia
Año de publicación
2019
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
17β-estradiol (E2) induces axonal growth through extracellular signal-regulated kinase 1 and 2 (ERK1/2)-MAPK cascade in hypothalamic neurons of male rat embryos in vitro, but the mechanism that initiates these events is poorly understood. This study reports the intracellular Ca2+ increase that participates in the activation of ERK1/2 and axogenesis induced by E2. Hypothalamic neuron cultures were established from 16-day-old male rat embryos and fed with astroglia-conditioned media for 48 h. E2-induced ERK phosphorylation was completely abolished by a ryanodine receptor (RyR) inhibitor (ryanodine) and partially attenuated by an L-type voltage-gated Ca2+ channel (L-VGCC) blocker (nifedipine), an inositol-1,4,5-trisphosphate receptor (IP3R) inhibitor (2-APB), and a phospholipase C (PLC) inhibitor (U-73122). We also conducted Ca2+ imaging recording using primary cultured neurons. The results show that E2 rapidly induces an increase in cytosolic Ca2+, which often occurs in repetitive Ca2+ oscillations. This response was not observed in the absence of extracellular Ca2+ or with inhibitory ryanodine and was markedly reduced by nifedipine. E2-induced axonal growth was completely inhibited by ryanodine. In summary, the results suggest that Ca2+ mobilization from extracellular space as well as from the endoplasmic reticulum is necessary for E2-induced ERK1/2 activation and axogenesis. Understanding the mechanisms of brain estrogenic actions might contribute to develop novel estrogen-based therapies for neurodegenerative diseases.
Fil: Cabrera Zapata, Lucas Ezequiel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra. Universidad Nacional de Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra; Argentina
Fil: Bollo, Mariana Ines. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra. Universidad Nacional de Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra; Argentina
Fil: Cambiasso, Maria Julia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra. Universidad Nacional de Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra; Argentina
Materia
AXOGENESIS
CALCIUM SIGNALING
ERK1/2
ESTRADIOL
HYPOTHALAMIC NEURONS
RYANODINE RECEPTORS
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:11336/128876
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/128876
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network_name_str CONICET Digital (CONICET)
spelling Estradiol-mediated axogenesis of hypothalamic neurons requires ERK1/2 and ryanodine receptors-dependent intracellular Ca2+ rise in male ratsCabrera Zapata, Lucas EzequielBollo, Mariana InesCambiasso, Maria JuliaAXOGENESISCALCIUM SIGNALINGERK1/2ESTRADIOLHYPOTHALAMIC NEURONSRYANODINE RECEPTORShttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/117β-estradiol (E2) induces axonal growth through extracellular signal-regulated kinase 1 and 2 (ERK1/2)-MAPK cascade in hypothalamic neurons of male rat embryos in vitro, but the mechanism that initiates these events is poorly understood. This study reports the intracellular Ca2+ increase that participates in the activation of ERK1/2 and axogenesis induced by E2. Hypothalamic neuron cultures were established from 16-day-old male rat embryos and fed with astroglia-conditioned media for 48 h. E2-induced ERK phosphorylation was completely abolished by a ryanodine receptor (RyR) inhibitor (ryanodine) and partially attenuated by an L-type voltage-gated Ca2+ channel (L-VGCC) blocker (nifedipine), an inositol-1,4,5-trisphosphate receptor (IP3R) inhibitor (2-APB), and a phospholipase C (PLC) inhibitor (U-73122). We also conducted Ca2+ imaging recording using primary cultured neurons. The results show that E2 rapidly induces an increase in cytosolic Ca2+, which often occurs in repetitive Ca2+ oscillations. This response was not observed in the absence of extracellular Ca2+ or with inhibitory ryanodine and was markedly reduced by nifedipine. E2-induced axonal growth was completely inhibited by ryanodine. In summary, the results suggest that Ca2+ mobilization from extracellular space as well as from the endoplasmic reticulum is necessary for E2-induced ERK1/2 activation and axogenesis. Understanding the mechanisms of brain estrogenic actions might contribute to develop novel estrogen-based therapies for neurodegenerative diseases.Fil: Cabrera Zapata, Lucas Ezequiel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra. Universidad Nacional de Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra; ArgentinaFil: Bollo, Mariana Ines. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra. Universidad Nacional de Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra; ArgentinaFil: Cambiasso, Maria Julia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra. Universidad Nacional de Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra; ArgentinaFrontiers Media S.A.2019-01info: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/11336/128876Cabrera Zapata, Lucas Ezequiel; Bollo, Mariana Ines; Cambiasso, Maria Julia; Estradiol-mediated axogenesis of hypothalamic neurons requires ERK1/2 and ryanodine receptors-dependent intracellular Ca2+ rise in male rats; Frontiers Media S.A.; Frontiers in Cellular Neuroscience; 13; 1-2019; 1-111662-5102CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.3389/fncel.2019.00122info:eu-repo/semantics/altIdentifier/url/https://www.frontiersin.org/articles/10.3389/fncel.2019.00122/fullinfo:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-10-22T11:25:31Zoai:ri.conicet.gov.ar:11336/128876instacron: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 11:25:31.401CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Estradiol-mediated axogenesis of hypothalamic neurons requires ERK1/2 and ryanodine receptors-dependent intracellular Ca2+ rise in male rats
title Estradiol-mediated axogenesis of hypothalamic neurons requires ERK1/2 and ryanodine receptors-dependent intracellular Ca2+ rise in male rats
spellingShingle Estradiol-mediated axogenesis of hypothalamic neurons requires ERK1/2 and ryanodine receptors-dependent intracellular Ca2+ rise in male rats
Cabrera Zapata, Lucas Ezequiel
AXOGENESIS
CALCIUM SIGNALING
ERK1/2
ESTRADIOL
HYPOTHALAMIC NEURONS
RYANODINE RECEPTORS
title_short Estradiol-mediated axogenesis of hypothalamic neurons requires ERK1/2 and ryanodine receptors-dependent intracellular Ca2+ rise in male rats
title_full Estradiol-mediated axogenesis of hypothalamic neurons requires ERK1/2 and ryanodine receptors-dependent intracellular Ca2+ rise in male rats
title_fullStr Estradiol-mediated axogenesis of hypothalamic neurons requires ERK1/2 and ryanodine receptors-dependent intracellular Ca2+ rise in male rats
title_full_unstemmed Estradiol-mediated axogenesis of hypothalamic neurons requires ERK1/2 and ryanodine receptors-dependent intracellular Ca2+ rise in male rats
title_sort Estradiol-mediated axogenesis of hypothalamic neurons requires ERK1/2 and ryanodine receptors-dependent intracellular Ca2+ rise in male rats
dc.creator.none.fl_str_mv Cabrera Zapata, Lucas Ezequiel
Bollo, Mariana Ines
Cambiasso, Maria Julia
author Cabrera Zapata, Lucas Ezequiel
author_facet Cabrera Zapata, Lucas Ezequiel
Bollo, Mariana Ines
Cambiasso, Maria Julia
author_role author
author2 Bollo, Mariana Ines
Cambiasso, Maria Julia
author2_role author
author
dc.subject.none.fl_str_mv AXOGENESIS
CALCIUM SIGNALING
ERK1/2
ESTRADIOL
HYPOTHALAMIC NEURONS
RYANODINE RECEPTORS
topic AXOGENESIS
CALCIUM SIGNALING
ERK1/2
ESTRADIOL
HYPOTHALAMIC NEURONS
RYANODINE RECEPTORS
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv 17β-estradiol (E2) induces axonal growth through extracellular signal-regulated kinase 1 and 2 (ERK1/2)-MAPK cascade in hypothalamic neurons of male rat embryos in vitro, but the mechanism that initiates these events is poorly understood. This study reports the intracellular Ca2+ increase that participates in the activation of ERK1/2 and axogenesis induced by E2. Hypothalamic neuron cultures were established from 16-day-old male rat embryos and fed with astroglia-conditioned media for 48 h. E2-induced ERK phosphorylation was completely abolished by a ryanodine receptor (RyR) inhibitor (ryanodine) and partially attenuated by an L-type voltage-gated Ca2+ channel (L-VGCC) blocker (nifedipine), an inositol-1,4,5-trisphosphate receptor (IP3R) inhibitor (2-APB), and a phospholipase C (PLC) inhibitor (U-73122). We also conducted Ca2+ imaging recording using primary cultured neurons. The results show that E2 rapidly induces an increase in cytosolic Ca2+, which often occurs in repetitive Ca2+ oscillations. This response was not observed in the absence of extracellular Ca2+ or with inhibitory ryanodine and was markedly reduced by nifedipine. E2-induced axonal growth was completely inhibited by ryanodine. In summary, the results suggest that Ca2+ mobilization from extracellular space as well as from the endoplasmic reticulum is necessary for E2-induced ERK1/2 activation and axogenesis. Understanding the mechanisms of brain estrogenic actions might contribute to develop novel estrogen-based therapies for neurodegenerative diseases.
Fil: Cabrera Zapata, Lucas Ezequiel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra. Universidad Nacional de Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra; Argentina
Fil: Bollo, Mariana Ines. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra. Universidad Nacional de Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra; Argentina
Fil: Cambiasso, Maria Julia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra. Universidad Nacional de Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra; Argentina
description 17β-estradiol (E2) induces axonal growth through extracellular signal-regulated kinase 1 and 2 (ERK1/2)-MAPK cascade in hypothalamic neurons of male rat embryos in vitro, but the mechanism that initiates these events is poorly understood. This study reports the intracellular Ca2+ increase that participates in the activation of ERK1/2 and axogenesis induced by E2. Hypothalamic neuron cultures were established from 16-day-old male rat embryos and fed with astroglia-conditioned media for 48 h. E2-induced ERK phosphorylation was completely abolished by a ryanodine receptor (RyR) inhibitor (ryanodine) and partially attenuated by an L-type voltage-gated Ca2+ channel (L-VGCC) blocker (nifedipine), an inositol-1,4,5-trisphosphate receptor (IP3R) inhibitor (2-APB), and a phospholipase C (PLC) inhibitor (U-73122). We also conducted Ca2+ imaging recording using primary cultured neurons. The results show that E2 rapidly induces an increase in cytosolic Ca2+, which often occurs in repetitive Ca2+ oscillations. This response was not observed in the absence of extracellular Ca2+ or with inhibitory ryanodine and was markedly reduced by nifedipine. E2-induced axonal growth was completely inhibited by ryanodine. In summary, the results suggest that Ca2+ mobilization from extracellular space as well as from the endoplasmic reticulum is necessary for E2-induced ERK1/2 activation and axogenesis. Understanding the mechanisms of brain estrogenic actions might contribute to develop novel estrogen-based therapies for neurodegenerative diseases.
publishDate 2019
dc.date.none.fl_str_mv 2019-01
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/11336/128876
Cabrera Zapata, Lucas Ezequiel; Bollo, Mariana Ines; Cambiasso, Maria Julia; Estradiol-mediated axogenesis of hypothalamic neurons requires ERK1/2 and ryanodine receptors-dependent intracellular Ca2+ rise in male rats; Frontiers Media S.A.; Frontiers in Cellular Neuroscience; 13; 1-2019; 1-11
1662-5102
CONICET Digital
CONICET
url http://hdl.handle.net/11336/128876
identifier_str_mv Cabrera Zapata, Lucas Ezequiel; Bollo, Mariana Ines; Cambiasso, Maria Julia; Estradiol-mediated axogenesis of hypothalamic neurons requires ERK1/2 and ryanodine receptors-dependent intracellular Ca2+ rise in male rats; Frontiers Media S.A.; Frontiers in Cellular Neuroscience; 13; 1-2019; 1-11
1662-5102
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.3389/fncel.2019.00122
info:eu-repo/semantics/altIdentifier/url/https://www.frontiersin.org/articles/10.3389/fncel.2019.00122/full
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
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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