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

Allopregnanolone (A) and pregnanolone (P) are able to modify 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 conta...

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Autores principales:	Rey, M., Kruse, M.S., Alvarez, L.D., Ghini, A.A., Veleiro, A.S., Burton, G., Coirini, H.
Formato:	JOUR
Materias:	3β-HSD Cerebellum Hippocampus Hypothalamus Hypoxia Neurosteroids 3alpha hydroxy 11alpha,19 epoxypregn 4 ene 20 one 3alpha hydroxy 1alpha,11alpha epoxy 5alpha pregnan 20 one 3alpha hydroxy 1alpha,11alpha epoxypregn 4 ene 20 one 3alpha hydroxy 1beta,11alpha epoxy 5alpha pregnan 20 one 3alpha hydroxy 2alpha,19 epoxy 5alpha pregnan 20 one 3alpha hydroxy 4alpha,19 epoxy 5alpha pregnan 20 one 3alpha hydroxy 5alpha pregnan 20 one 3alpha hydroxy 6,19 epoxypregn 4 ene 20 one 4 aminobutyric acid A receptor eltanolone flunitrazepam glial fibrillary acidic protein muscimol steroid unclassified drug animal experiment animal tissue article astrocytosis binding affinity binding site brain cortex brain hypoxia brain region cerebellum controlled study drug efficacy drug mechanism drug receptor binding drug response drug structure enzyme activity hippocampus hypoxia ligand binding male mouse neurofilament neuroprotection nonhuman priority journal rat Animals Dose-Response Relationship, Drug Male Neuroprotective Agents Organ Culture Techniques Oxygen Protein Binding Rats Rats, Sprague-Dawley Receptors, GABA-A Steroids
Acceso en línea:	http://hdl.handle.net/20.500.12110/paper_00144886_v249_n_p49_Rey
Aporte de:	Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) de Universidad de Buenos Aires

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spelling	todo:paper_00144886_v249_n_p49_Rey2023-10-03T14:12:45Z Neuroprotective action of synthetic steroids with oxygen bridge. Activity on GABAA receptor Rey, M. Kruse, M.S. Alvarez, L.D. Ghini, A.A. Veleiro, A.S. Burton, G. Coirini, H. 3β-HSD Cerebellum Hippocampus Hypothalamus Hypoxia Neurosteroids 3alpha hydroxy 11alpha,19 epoxypregn 4 ene 20 one 3alpha hydroxy 1alpha,11alpha epoxy 5alpha pregnan 20 one 3alpha hydroxy 1alpha,11alpha epoxypregn 4 ene 20 one 3alpha hydroxy 1beta,11alpha epoxy 5alpha pregnan 20 one 3alpha hydroxy 2alpha,19 epoxy 5alpha pregnan 20 one 3alpha hydroxy 4alpha,19 epoxy 5alpha pregnan 20 one 3alpha hydroxy 5alpha pregnan 20 one 3alpha hydroxy 6,19 epoxypregn 4 ene 20 one 4 aminobutyric acid A receptor eltanolone flunitrazepam glial fibrillary acidic protein muscimol steroid unclassified drug animal experiment animal tissue article astrocytosis binding affinity binding site brain cortex brain hypoxia brain region cerebellum controlled study drug efficacy drug mechanism drug receptor binding drug response drug structure enzyme activity hippocampus hypoxia ligand binding male mouse neurofilament neuroprotection nonhuman priority journal rat 3β-HSD Cerebellum Hippocampus Hypothalamus Hypoxia Neurosteroids Animals Dose-Response Relationship, Drug Hippocampus Male Neuroprotective Agents Organ Culture Techniques Oxygen Protein Binding Rats Rats, Sprague-Dawley Receptors, GABA-A Steroids Allopregnanolone (A) and pregnanolone (P) are able to modify 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]-flunitrazepam and reduced [35S]-TBPS binding. The enzyme 3β-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 SS was evaluated in cerebral cortex and hippocampus cultures subjected to hypoxia. Glial fibrillary acidic protein (GFAP) increase was 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 prevented microtubule 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. © 2013 Elsevier Inc. Fil:Rey, M. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Alvarez, L.D. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Ghini, A.A. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Veleiro, A.S. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Burton, G. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Coirini, H. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. JOUR info:eu-repo/semantics/openAccess http://creativecommons.org/licenses/by/2.5/ar http://hdl.handle.net/20.500.12110/paper_00144886_v249_n_p49_Rey
institution	Universidad de Buenos Aires
institution_str	I-28
repository_str	R-134
collection	Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA)
topic	3β-HSD Cerebellum Hippocampus Hypothalamus Hypoxia Neurosteroids 3alpha hydroxy 11alpha,19 epoxypregn 4 ene 20 one 3alpha hydroxy 1alpha,11alpha epoxy 5alpha pregnan 20 one 3alpha hydroxy 1alpha,11alpha epoxypregn 4 ene 20 one 3alpha hydroxy 1beta,11alpha epoxy 5alpha pregnan 20 one 3alpha hydroxy 2alpha,19 epoxy 5alpha pregnan 20 one 3alpha hydroxy 4alpha,19 epoxy 5alpha pregnan 20 one 3alpha hydroxy 5alpha pregnan 20 one 3alpha hydroxy 6,19 epoxypregn 4 ene 20 one 4 aminobutyric acid A receptor eltanolone flunitrazepam glial fibrillary acidic protein muscimol steroid unclassified drug animal experiment animal tissue article astrocytosis binding affinity binding site brain cortex brain hypoxia brain region cerebellum controlled study drug efficacy drug mechanism drug receptor binding drug response drug structure enzyme activity hippocampus hypoxia ligand binding male mouse neurofilament neuroprotection nonhuman priority journal rat 3β-HSD Cerebellum Hippocampus Hypothalamus Hypoxia Neurosteroids Animals Dose-Response Relationship, Drug Hippocampus Male Neuroprotective Agents Organ Culture Techniques Oxygen Protein Binding Rats Rats, Sprague-Dawley Receptors, GABA-A Steroids
spellingShingle	3β-HSD Cerebellum Hippocampus Hypothalamus Hypoxia Neurosteroids 3alpha hydroxy 11alpha,19 epoxypregn 4 ene 20 one 3alpha hydroxy 1alpha,11alpha epoxy 5alpha pregnan 20 one 3alpha hydroxy 1alpha,11alpha epoxypregn 4 ene 20 one 3alpha hydroxy 1beta,11alpha epoxy 5alpha pregnan 20 one 3alpha hydroxy 2alpha,19 epoxy 5alpha pregnan 20 one 3alpha hydroxy 4alpha,19 epoxy 5alpha pregnan 20 one 3alpha hydroxy 5alpha pregnan 20 one 3alpha hydroxy 6,19 epoxypregn 4 ene 20 one 4 aminobutyric acid A receptor eltanolone flunitrazepam glial fibrillary acidic protein muscimol steroid unclassified drug animal experiment animal tissue article astrocytosis binding affinity binding site brain cortex brain hypoxia brain region cerebellum controlled study drug efficacy drug mechanism drug receptor binding drug response drug structure enzyme activity hippocampus hypoxia ligand binding male mouse neurofilament neuroprotection nonhuman priority journal rat 3β-HSD Cerebellum Hippocampus Hypothalamus Hypoxia Neurosteroids Animals Dose-Response Relationship, Drug Hippocampus Male Neuroprotective Agents Organ Culture Techniques Oxygen Protein Binding Rats Rats, Sprague-Dawley Receptors, GABA-A Steroids Rey, M. Kruse, M.S. Alvarez, L.D. Ghini, A.A. Veleiro, A.S. Burton, G. Coirini, H. Neuroprotective action of synthetic steroids with oxygen bridge. Activity on GABAA receptor
topic_facet	3β-HSD Cerebellum Hippocampus Hypothalamus Hypoxia Neurosteroids 3alpha hydroxy 11alpha,19 epoxypregn 4 ene 20 one 3alpha hydroxy 1alpha,11alpha epoxy 5alpha pregnan 20 one 3alpha hydroxy 1alpha,11alpha epoxypregn 4 ene 20 one 3alpha hydroxy 1beta,11alpha epoxy 5alpha pregnan 20 one 3alpha hydroxy 2alpha,19 epoxy 5alpha pregnan 20 one 3alpha hydroxy 4alpha,19 epoxy 5alpha pregnan 20 one 3alpha hydroxy 5alpha pregnan 20 one 3alpha hydroxy 6,19 epoxypregn 4 ene 20 one 4 aminobutyric acid A receptor eltanolone flunitrazepam glial fibrillary acidic protein muscimol steroid unclassified drug animal experiment animal tissue article astrocytosis binding affinity binding site brain cortex brain hypoxia brain region cerebellum controlled study drug efficacy drug mechanism drug receptor binding drug response drug structure enzyme activity hippocampus hypoxia ligand binding male mouse neurofilament neuroprotection nonhuman priority journal rat 3β-HSD Cerebellum Hippocampus Hypothalamus Hypoxia Neurosteroids Animals Dose-Response Relationship, Drug Hippocampus Male Neuroprotective Agents Organ Culture Techniques Oxygen Protein Binding Rats Rats, Sprague-Dawley Receptors, GABA-A Steroids
description	Allopregnanolone (A) and pregnanolone (P) are able to modify 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]-flunitrazepam and reduced [35S]-TBPS binding. The enzyme 3β-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 SS was evaluated in cerebral cortex and hippocampus cultures subjected to hypoxia. Glial fibrillary acidic protein (GFAP) increase was 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 prevented microtubule 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. © 2013 Elsevier Inc.
format	JOUR
author	Rey, M. Kruse, M.S. Alvarez, L.D. Ghini, A.A. Veleiro, A.S. Burton, G. Coirini, H.
author_facet	Rey, M. Kruse, M.S. Alvarez, L.D. Ghini, A.A. Veleiro, A.S. Burton, G. Coirini, H.
author_sort	Rey, M.
title	Neuroprotective action of synthetic steroids with oxygen bridge. Activity on GABAA receptor
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
url	http://hdl.handle.net/20.500.12110/paper_00144886_v249_n_p49_Rey
work_keys_str_mv	AT reym neuroprotectiveactionofsyntheticsteroidswithoxygenbridgeactivityongabaareceptor AT krusems neuroprotectiveactionofsyntheticsteroidswithoxygenbridgeactivityongabaareceptor AT alvarezld neuroprotectiveactionofsyntheticsteroidswithoxygenbridgeactivityongabaareceptor AT ghiniaa neuroprotectiveactionofsyntheticsteroidswithoxygenbridgeactivityongabaareceptor AT veleiroas neuroprotectiveactionofsyntheticsteroidswithoxygenbridgeactivityongabaareceptor AT burtong neuroprotectiveactionofsyntheticsteroidswithoxygenbridgeactivityongabaareceptor AT coirinih neuroprotectiveactionofsyntheticsteroidswithoxygenbridgeactivityongabaareceptor
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Neuroprotective action of synthetic steroids with oxygen bridge. Activity on GABAA receptor

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