Artículo

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" (2013) Experimental Neurology. 249:49-58
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Abstract:

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.

Registro:

Documento: Artículo
Título:Neuroprotective action of synthetic steroids with oxygen bridge. Activity on GABAA receptor
Autor:Rey, M.; Kruse, M.S.; Alvarez, L.D.; Ghini, A.A.; Veleiro, A.S.; Burton, G.; Coirini, H.
Filiación:Laboratorio de Neurobiología, Instituto de Biología y Medicina Experimental (IBYME-CONICET), Vuelta de Obligado 2490, C1428ADN Ciudad Autónoma de Buenos Aires, Argentina
Departamento de Química Orgánica, Unidad de Microanálisis y Metodos Fisicos aplicados a Quimica Organica (UMYMFOR-CONICET), Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires (FCEN-UBA), Pabellon 2, Ciudad Univ., Intendente Guiraldes 2160, C1428EHA Ciudad Autónoma de Buenos Aires, Argentina
Departamento de Bioquímica Humana, Facultad de Medicina, Universidad de Buenos Aires, Paraguay 2155, 5to Piso, C1121ABG Ciudad Autónoma de Buenos Aires, Argentina
Palabras clave: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
Año:2013
Volumen:249
Página de inicio:49
Página de fin:58
DOI: http://dx.doi.org/10.1016/j.expneurol.2013.07.020
Título revista:Experimental Neurology
Título revista abreviado:Exp. Neurol.
ISSN:00144886
CODEN:EXNEA
CAS:3alpha hydroxy 5alpha pregnan 20 one, 516-54-1; eltanolone, 128-20-1; flunitrazepam, 1622-62-4; muscimol, 2763-96-4; Neuroprotective Agents; Oxygen, S88TT14065; Receptors, GABA-A; Steroids
Registro:https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00144886_v249_n_p49_Rey

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Citas:

---------- APA ----------
Rey, M., Kruse, M.S., Alvarez, L.D., Ghini, A.A., Veleiro, A.S., Burton, G. & Coirini, H. (2013) . Neuroprotective action of synthetic steroids with oxygen bridge. Activity on GABAA receptor. Experimental Neurology, 249, 49-58.
http://dx.doi.org/10.1016/j.expneurol.2013.07.020
---------- CHICAGO ----------
Rey, M., Kruse, M.S., Alvarez, L.D., Ghini, A.A., Veleiro, A.S., Burton, G., et al. "Neuroprotective action of synthetic steroids with oxygen bridge. Activity on GABAA receptor" . Experimental Neurology 249 (2013) : 49-58.
http://dx.doi.org/10.1016/j.expneurol.2013.07.020
---------- MLA ----------
Rey, M., Kruse, M.S., Alvarez, L.D., Ghini, A.A., Veleiro, A.S., Burton, G., et al. "Neuroprotective action of synthetic steroids with oxygen bridge. Activity on GABAA receptor" . Experimental Neurology, vol. 249, 2013, pp. 49-58.
http://dx.doi.org/10.1016/j.expneurol.2013.07.020
---------- VANCOUVER ----------
Rey, M., Kruse, M.S., Alvarez, L.D., Ghini, A.A., Veleiro, A.S., Burton, G., et al. Neuroprotective action of synthetic steroids with oxygen bridge. Activity on GABAA receptor. Exp. Neurol. 2013;249:49-58.
http://dx.doi.org/10.1016/j.expneurol.2013.07.020