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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Acceso en línea: | https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00144886_v249_n_p49_Rey http://hdl.handle.net/20.500.12110/paper_00144886_v249_n_p49_Rey |
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paper:paper_00144886_v249_n_p49_Rey2023-06-08T14:37:21Z Neuroprotective action of synthetic steroids with oxygen bridge. Activity on GABAA receptor Rey, Mariana Alvarez, Lautaro Damián Ghini, Alberto Antonio Veleiro, Adriana Silvia Burton, Gerardo Coirini, Héctor 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. 2013 https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00144886_v249_n_p49_Rey 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, Mariana Alvarez, Lautaro Damián Ghini, Alberto Antonio Veleiro, Adriana Silvia Burton, Gerardo Coirini, Héctor 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. |
author |
Rey, Mariana Alvarez, Lautaro Damián Ghini, Alberto Antonio Veleiro, Adriana Silvia Burton, Gerardo Coirini, Héctor |
author_facet |
Rey, Mariana Alvarez, Lautaro Damián Ghini, Alberto Antonio Veleiro, Adriana Silvia Burton, Gerardo Coirini, Héctor |
author_sort |
Rey, Mariana |
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 |
publishDate |
2013 |
url |
https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00144886_v249_n_p49_Rey http://hdl.handle.net/20.500.12110/paper_00144886_v249_n_p49_Rey |
work_keys_str_mv |
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1768546143516491776 |