Artículo
Neuroprotective action of synthetic steroids with oxygen bridge. Activity on GABAA receptor
Rey, Mariana
; Kruse, Maria Sol
; Alvarez, Lautaro Damian
; Ghini, Alberto Antonio
; Veleiro, Adriana Silvia
; Burton, Gerardo
; Coirini, Hector
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Fecha de publicación:
08/2013
Editorial:
Elsevier
Revista:
Experimental Neurology
ISSN:
0014-4886
Idioma:
Inglés
Tipo de recurso:
Artículo publicado
Clasificación temática:
Resumen
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.
Palabras clave:
Neurosteroids
,
3b-Hsd
,
Hypoxia
,
Hyppocampus
,
Hypothalamus
,
Cerebellum
Archivos asociados
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Identificadores
Colecciones
Articulos(IBYME)
Articulos de INST.DE BIOLOGIA Y MEDICINA EXPERIMENTAL (I)
Articulos de INST.DE BIOLOGIA Y MEDICINA EXPERIMENTAL (I)
Articulos(SEDE CENTRAL)
Articulos de SEDE CENTRAL
Articulos de SEDE CENTRAL
Articulos(UMYMFOR)
Articulos de UNID.MICROANAL.Y MET.FISICOS EN QUIM.ORG.(I)
Articulos de UNID.MICROANAL.Y MET.FISICOS EN QUIM.ORG.(I)
Citación
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
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