期刊
EXPERIMENTAL NEUROLOGY
卷 249, 期 -, 页码 49-58出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.expneurol.2013.07.020
关键词
Neurosteroids; 3 beta-HSD; Hypoxia; Hippocampus; Hypothalamus; Cerebellum
Allopregnanolone (A) and pregnanolone (P) are able to modify neural activities acting through the GABA(A) 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 [H-3]-flunitrazepam and reduced [S-35]-TBPS binding. The enzyme 3 beta-hydroxysteroid dehydrogenase (3 beta-HSD) produces the precursor for A and P, and its activity is regulated by steroids. The action of several SS on 3 beta-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. (C) 2013 Elsevier Inc. All rights reserved.
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