Effect of chronic administration of estradiol, progesterone, and tibolone on the expression and phosphorylation of glycogen synthase kinase-3ß and the microtubule-associated protein tau in the hippocampus and cerebellum of female rat.
J Neurosci Res
; 90(4): 878-86, 2012 Apr.
Article
en En
| MEDLINE
| ID: mdl-22183707
Gonadal hormones regulate expression and activation of protein tau. Tibolone is a drug used as first- choice comprehensive treatment for the relief of menopausal symptoms, because it and its various metabolites have estrogenic properties and progestogenic/androgenic effects; however, the effect on the activation of tau protein and its signaling cascade in the brain is unknown. We studied the effect of chronic administration of estradiol (E2), progesterone (P4), and tibolone (TIB) on the expression and phosphorylation of microtubule-associated protein tau and glycogen synthase kinase-3ß (GSK3ß) in the hippocampus and cerebellum of ovariectomized rats. Ovariectomized adult female rats were implanted with pellets of vehicle, E2, or P4 or were treated with TIB by oral administration for 60 days. The animals were sacrificed, and tissue proteins were analyzed by Western blot. We observed that, in the hippocampus, administration of E2, P4, or TIB significantly decreased the protein content of hyperphosphorylated tau and increased the tau dephosphorylated form, whereas only treatment with TIB increased the content of the phosphorylated form of GSK3ß. In the cerebellum, E2 and TIB treatments resulted in a significant decrease in the expression of hyperphosphorylated tau, whereas E2 and TIB increased phosphorylated GSK3ß; P4 had no effect. These results indicate that chronic administration of gonadal hormones and tibolone modulates tau and GSK3ß phosphorylation in hippocampus and cerebellum of the rat and may exert a neuroprotective effect in these tissues.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Cerebelo
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Proteínas tau
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Glucógeno Sintasa Quinasa 3
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Hormonas Gonadales
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Hipocampo
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Antagonistas de Andrógenos
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Norpregnenos
Tipo de estudio:
Risk_factors_studies
Límite:
Animals
Idioma:
En
Revista:
J Neurosci Res
Año:
2012
Tipo del documento:
Article
Pais de publicación:
Estados Unidos