RESUMO
AIMS: The aim of the present study was to investigate the effects of different periods of ovariectomy and 17beta-estradiol replacement on apoptotic cell death and expression of members of the Bcl-2 family in the rat hippocampus. MAIN METHODS: Hippocampi were obtained from rats in proestrus, ovariectomized (15 days, 21 days and 36 days), ovariectomized for 15 days and then treated with 17beta-estradiol for 7 or 21 days, and rats ovariectomized and immediately treated with 17beta-estradiol for 21 days. The expression of Bcl-2 and Bax and the number of apoptotic cells were determined. KEY FINDINGS: Ovariectomy decreased Bcl-2 expression and increased Bax expression and the number of apoptotic cells. Replacement with 17beta-estradiol (21 days) throughout the post-ovariectomy period reduced the number of apoptotic cells to the control levels, and prevented the effects of ovariectomy on Bax expression, but only partially restored the Bcl-2 expression. After 15 days of ovariectomy, the replacement with 17beta-estradiol for 21 days, but not for 7 days, restored the Bcl-2 and Bax expression and the percentage of apoptotic cells to the levels found in the proestrus control. SIGNIFICANCE: The present results show that a physiological concentration of 17beta-estradiol may help maintain long-term neuronal viability by regulating the expression of members of the Bcl-2 family. Even after a period of hormonal deprivation, treatment with 17beta-estradiol is able to restore the expression of Bax and Bcl-2 to control levels, but the duration of the treatment is a key factor to obtain the desired effect. These data provide new understanding into the mechanisms contributing to the neuroprotective action of estrogen.
Assuntos
Apoptose/efeitos dos fármacos , Estradiol/farmacologia , Hipocampo/efeitos dos fármacos , Ovariectomia/efeitos adversos , Animais , Apoptose/fisiologia , Western Blotting , Feminino , Hipocampo/química , Hipocampo/fisiopatologia , Proteínas Proto-Oncogênicas c-bcl-2/análise , Ratos , Ratos Wistar , Proteína X Associada a bcl-2/análiseRESUMO
The aim of the present study was to investigate the effects of different periods of ovariectomy and 17â- estradiol replacement on apoptotic cell death and expression of members of the Bcl-2 family in the rat hippocampus. Hippocampi were obtained from rats in proestrus, ovariectomized (15 days, 21 days and 36 days), ovariectomized for 15 days and then treated with 17â-estradiol for 7 or 21 days, and rats ovariectomized and immediately treated with 17â-estradiol for 21 days. The expression of Bcl-2 and Bax and the number of apoptotic cells were determined. Ovariectomy decreased Bcl-2 expression and increased Bax expression and the number of apoptotic cells. Replacement with 17â-estradiol (21 days) throughout the post-ovariectomy period reduced the number of apoptotic cells to the control levels, and prevented the effects of ovariectomy on Baxexpression, but only partially restored the Bcl-2 expression. After 15 days of ovariectomy, the replacementwith 17â-estradiol for 21 days, but not for 7 days, restored the Bcl-2 and Bax expression and the percentageof apoptotic cells to the levels found in the proestrus control.The present results show that a physiological concentration of 17â-estradiol my help maintainlong-term neuronal viability by regulating the expression of members of the Bcl-2 family. Even after a period of hormonal deprivation, treatment with 17â-estradiol is able to restore the expression of Bax and Bcl-2 to control levels, but the duration of the treatment is a key factor to obtain the desired effect. These dataprovide new understanding into the mechanisms contributing to the neuroprotective action of estrogen.