Neuroprotective action of synthetic steroids with oxygen bridge. Activity on GABAA receptor

Autores
Rey, Mariana; Kruse, Maria Sol; Alvarez, Lautaro Damian; Ghini, Alberto Antonio; Veleiro, Adriana Silvia; Burton, Gerardo; Coirini, Hector
Año de publicación
2013
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Allopregnanolone (A) and pregnanolone (P) are able tomodify neural activities acting through the GABAA receptor complex. This capacity makes them useful as anticonvulsant, anxiolytic, or  anti-stress compounds. In this study, the performance of seven synthetic steroids (SS) analogous of A or P containing an intramolecular oxygen bridge was evaluated using different assays. Competition assays showed that compounds 1, 5, 6 and 7 affected the binding of specific ligands for the GABAA receptor in a way similar to that of A and P, whereas compounds 3 and 4 stimulated [3H]-flunitrazepamand reduced [35S]-TBPS binding. The enzyme3β-hydroxysteroid dehydrogenase (3β-HSD) produces the precursor for A and P, and its activity is regulated by steroids. The action of several SS on 3β-HSD activity was tested in different tissues. All SS analyzed inhibit its activity, but compound 5 was the least effective. Finally, the neuroprotective role of two SSwas evaluated in cerebral cortex and hippocampus cultures subjected to hypoxia. Glial fibrillary acidic protein (GFAP) increasewas prevented by A, P, and compounds 3 and 5. Only A, P and compound 5 prevented neurofilament (NF160/200) decrease in hippocampus cultures,
whereas A and compound 5 partially prevented NF200 and NF160 decreases respectively in cerebral cortex cultures. A preventedmicrotubule associated protein (MAP 2b) decrease in cerebral cortex cultures,while in hippocampus cultures only compounds 3 and 5 had effect. All steroids prevented MAP 2c decrease in both brain regions.
Fil: Rey, Mariana. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina
Fil: Kruse, Maria Sol. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina
Fil: Alvarez, Lautaro Damian. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Unidad de Microanálisis y Métodos Físicos Aplicados A la Química Orgánica (i); Argentina
Fil: Ghini, Alberto Antonio. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Unidad de Microanálisis y Métodos Físicos Aplicados A la Química Orgánica (i); Argentina
Fil: Veleiro, Adriana Silvia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Unidad de Microanálisis y Métodos Físicos Aplicados A la Química Orgánica (i); Argentina
Fil: Burton, Gerardo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Unidad de Microanálisis y Métodos Físicos Aplicados A la Química Orgánica (i); Argentina
Fil: Coirini, Hector. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina
Materia
Neurosteroids
3b-Hsd
Hypoxia
Hyppocampus
Hypothalamus
Cerebellum
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:11336/7354
Acceder
id CONICETDig_198d77579ebf90f57e8af7a422fdd1b4
oai_identifier_str oai:ri.conicet.gov.ar:11336/7354
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Neuroprotective action of synthetic steroids with oxygen bridge. Activity on GABAA receptorRey, MarianaKruse, Maria SolAlvarez, Lautaro DamianGhini, Alberto AntonioVeleiro, Adriana SilviaBurton, GerardoCoirini, HectorNeurosteroids3b-HsdHypoxiaHyppocampusHypothalamusCerebellumhttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3Allopregnanolone (A) and pregnanolone (P) are able tomodify neural activities acting through the GABAA receptor complex. This capacity makes them useful as anticonvulsant, anxiolytic, or  anti-stress compounds. In this study, the performance of seven synthetic steroids (SS) analogous of A or P containing an intramolecular oxygen bridge was evaluated using different assays. Competition assays showed that compounds 1, 5, 6 and 7 affected the binding of specific ligands for the GABAA receptor in a way similar to that of A and P, whereas compounds 3 and 4 stimulated [3H]-flunitrazepamand reduced [35S]-TBPS binding. The enzyme3β-hydroxysteroid dehydrogenase (3β-HSD) produces the precursor for A and P, and its activity is regulated by steroids. The action of several SS on 3β-HSD activity was tested in different tissues. All SS analyzed inhibit its activity, but compound 5 was the least effective. Finally, the neuroprotective role of two SSwas evaluated in cerebral cortex and hippocampus cultures subjected to hypoxia. Glial fibrillary acidic protein (GFAP) increasewas prevented by A, P, and compounds 3 and 5. Only A, P and compound 5 prevented neurofilament (NF160/200) decrease in hippocampus cultures,<br />whereas A and compound 5 partially prevented NF200 and NF160 decreases respectively in cerebral cortex cultures. A preventedmicrotubule associated protein (MAP 2b) decrease in cerebral cortex cultures,while in hippocampus cultures only compounds 3 and 5 had effect. All steroids prevented MAP 2c decrease in both brain regions.Fil: Rey, Mariana. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); ArgentinaFil: Kruse, Maria Sol. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); ArgentinaFil: Alvarez, Lautaro Damian. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Unidad de Microanálisis y Métodos Físicos Aplicados A la Química Orgánica (i); ArgentinaFil: Ghini, Alberto Antonio. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Unidad de Microanálisis y Métodos Físicos Aplicados A la Química Orgánica (i); ArgentinaFil: Veleiro, Adriana Silvia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Unidad de Microanálisis y Métodos Físicos Aplicados A la Química Orgánica (i); ArgentinaFil: Burton, Gerardo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Unidad de Microanálisis y Métodos Físicos Aplicados A la Química Orgánica (i); ArgentinaFil: Coirini, Hector. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); ArgentinaElsevier2013-08info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/7354Rey, Mariana; Kruse, Maria Sol; Alvarez, Lautaro Damian; Ghini, Alberto Antonio; Veleiro, Adriana Silvia; et al.; Neuroprotective action of synthetic steroids with oxygen bridge. Activity on GABAA receptor; Elsevier; Experimental Neurology; 249; 8-2013; 49-580014-4886enginfo:eu-repo/semantics/altIdentifier/url/http://www.sciencedirect.com/science/article/pii/S0014488613002379info:eu-repo/semantics/altIdentifier/doi/10.1016/j.expneurol.2013.07.020info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T09:40:46Zoai:ri.conicet.gov.ar:11336/7354instacron: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:34982025-09-29 09:40:46.832CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Neuroprotective action of synthetic steroids with oxygen bridge. Activity on GABAA receptor
title Neuroprotective action of synthetic steroids with oxygen bridge. Activity on GABAA receptor
spellingShingle Neuroprotective action of synthetic steroids with oxygen bridge. Activity on GABAA receptor
Rey, Mariana
Neurosteroids
3b-Hsd
Hypoxia
Hyppocampus
Hypothalamus
Cerebellum
title_short Neuroprotective action of synthetic steroids with oxygen bridge. Activity on GABAA receptor
title_full Neuroprotective action of synthetic steroids with oxygen bridge. Activity on GABAA receptor
title_fullStr Neuroprotective action of synthetic steroids with oxygen bridge. Activity on GABAA receptor
title_full_unstemmed Neuroprotective action of synthetic steroids with oxygen bridge. Activity on GABAA receptor
title_sort Neuroprotective action of synthetic steroids with oxygen bridge. Activity on GABAA receptor
dc.creator.none.fl_str_mv Rey, Mariana
Kruse, Maria Sol
Alvarez, Lautaro Damian
Ghini, Alberto Antonio
Veleiro, Adriana Silvia
Burton, Gerardo
Coirini, Hector
author Rey, Mariana
author_facet Rey, Mariana
Kruse, Maria Sol
Alvarez, Lautaro Damian
Ghini, Alberto Antonio
Veleiro, Adriana Silvia
Burton, Gerardo
Coirini, Hector
author_role author
author2 Kruse, Maria Sol
Alvarez, Lautaro Damian
Ghini, Alberto Antonio
Veleiro, Adriana Silvia
Burton, Gerardo
Coirini, Hector
author2_role author
author
author
author
author
author
dc.subject.none.fl_str_mv Neurosteroids
3b-Hsd
Hypoxia
Hyppocampus
Hypothalamus
Cerebellum
topic Neurosteroids
3b-Hsd
Hypoxia
Hyppocampus
Hypothalamus
Cerebellum
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Allopregnanolone (A) and pregnanolone (P) are able tomodify neural activities acting through the GABAA receptor complex. This capacity makes them useful as anticonvulsant, anxiolytic, or  anti-stress compounds. In this study, the performance of seven synthetic steroids (SS) analogous of A or P containing an intramolecular oxygen bridge was evaluated using different assays. Competition assays showed that compounds 1, 5, 6 and 7 affected the binding of specific ligands for the GABAA receptor in a way similar to that of A and P, whereas compounds 3 and 4 stimulated [3H]-flunitrazepamand reduced [35S]-TBPS binding. The enzyme3β-hydroxysteroid dehydrogenase (3β-HSD) produces the precursor for A and P, and its activity is regulated by steroids. The action of several SS on 3β-HSD activity was tested in different tissues. All SS analyzed inhibit its activity, but compound 5 was the least effective. Finally, the neuroprotective role of two SSwas evaluated in cerebral cortex and hippocampus cultures subjected to hypoxia. Glial fibrillary acidic protein (GFAP) increasewas prevented by A, P, and compounds 3 and 5. Only A, P and compound 5 prevented neurofilament (NF160/200) decrease in hippocampus cultures,<br />whereas A and compound 5 partially prevented NF200 and NF160 decreases respectively in cerebral cortex cultures. A preventedmicrotubule associated protein (MAP 2b) decrease in cerebral cortex cultures,while in hippocampus cultures only compounds 3 and 5 had effect. All steroids prevented MAP 2c decrease in both brain regions.
Fil: Rey, Mariana. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina
Fil: Kruse, Maria Sol. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina
Fil: Alvarez, Lautaro Damian. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Unidad de Microanálisis y Métodos Físicos Aplicados A la Química Orgánica (i); Argentina
Fil: Ghini, Alberto Antonio. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Unidad de Microanálisis y Métodos Físicos Aplicados A la Química Orgánica (i); Argentina
Fil: Veleiro, Adriana Silvia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Unidad de Microanálisis y Métodos Físicos Aplicados A la Química Orgánica (i); Argentina
Fil: Burton, Gerardo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Unidad de Microanálisis y Métodos Físicos Aplicados A la Química Orgánica (i); Argentina
Fil: Coirini, Hector. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina
description Allopregnanolone (A) and pregnanolone (P) are able tomodify neural activities acting through the GABAA receptor complex. This capacity makes them useful as anticonvulsant, anxiolytic, or  anti-stress compounds. In this study, the performance of seven synthetic steroids (SS) analogous of A or P containing an intramolecular oxygen bridge was evaluated using different assays. Competition assays showed that compounds 1, 5, 6 and 7 affected the binding of specific ligands for the GABAA receptor in a way similar to that of A and P, whereas compounds 3 and 4 stimulated [3H]-flunitrazepamand reduced [35S]-TBPS binding. The enzyme3β-hydroxysteroid dehydrogenase (3β-HSD) produces the precursor for A and P, and its activity is regulated by steroids. The action of several SS on 3β-HSD activity was tested in different tissues. All SS analyzed inhibit its activity, but compound 5 was the least effective. Finally, the neuroprotective role of two SSwas evaluated in cerebral cortex and hippocampus cultures subjected to hypoxia. Glial fibrillary acidic protein (GFAP) increasewas prevented by A, P, and compounds 3 and 5. Only A, P and compound 5 prevented neurofilament (NF160/200) decrease in hippocampus cultures,<br />whereas A and compound 5 partially prevented NF200 and NF160 decreases respectively in cerebral cortex cultures. A preventedmicrotubule associated protein (MAP 2b) decrease in cerebral cortex cultures,while in hippocampus cultures only compounds 3 and 5 had effect. All steroids prevented MAP 2c decrease in both brain regions.
publishDate 2013
dc.date.none.fl_str_mv 2013-08
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/11336/7354
Rey, Mariana; Kruse, Maria Sol; Alvarez, Lautaro Damian; Ghini, Alberto Antonio; Veleiro, Adriana Silvia; et al.; Neuroprotective action of synthetic steroids with oxygen bridge. Activity on GABAA receptor; Elsevier; Experimental Neurology; 249; 8-2013; 49-58
0014-4886
url http://hdl.handle.net/11336/7354
identifier_str_mv Rey, Mariana; Kruse, Maria Sol; Alvarez, Lautaro Damian; Ghini, Alberto Antonio; Veleiro, Adriana Silvia; et al.; Neuroprotective action of synthetic steroids with oxygen bridge. Activity on GABAA receptor; Elsevier; Experimental Neurology; 249; 8-2013; 49-58
0014-4886
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/http://www.sciencedirect.com/science/article/pii/S0014488613002379
info:eu-repo/semantics/altIdentifier/doi/10.1016/j.expneurol.2013.07.020
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
application/pdf
application/pdf
application/pdf
application/pdf
dc.publisher.none.fl_str_mv Elsevier
publisher.none.fl_str_mv Elsevier
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 13.070432

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