Relationship Between ERR Subtypes Expressions In Peripheral Blood Mononuclear Cells And Estrogen Therapy Effects In Postmenopausal Women With Severe Vascular Dementia

Objective: To explore the relationship between estrogen receptor-related receptor (ERR)α,β,γexpressions in peripheral blood mononuclear cells and estrogen therapeutic effect in severe VD patients.Methods: Take 40 patients with severe VD who were effective to estrogen therapy as the test group, and another 40 patients with severe VD who failed to estrogen therapy as the control group. Reverse transcription polymerase chain reaction was used to detect the mRNA of various subtypes of ERR family and western blot was applied to determine the protein expression of ERR. We diagnosed the severe VD with Mini-mental state examination (MMSE-R) and clinical dementia rating table.Results:1. Serum estradiol level was significantly lower in elderly women patients of vascular dementia than healthy controls with correspondencing age and gender, and estrogen replacement therapy could increase serum estradiol levels.2. Serum estradiol levels in vascular dementia patient were associated with diabetes, and were markedly higher in patients with diabetes than those in patients without diabetes before and after estrogen treatment.3. RT-PCR and Western Blot analysis showed: there was a unique expression pattern in the mRNA and protein expressions of ERRα,βandγin the VD patients. ERRαmRNA and protein expression was lower in the ineffective group and higher in the effective group, but the levels of ERRαmRNA and protein both in ineffective group and effective group were lower that those in the healthy control group. ERRβshowed no significant differences among the effective group, ineffective group and healthy control. ERRγexpression was higher in ineffective group and lower in the effective group and was the lowest expression in healthy control. Conclusion: Compared with normal controls, the postmenopausal vascular dementia patients shows lower ERRαexpression and higher ERRγexpression in peripheral blood mononuclear cells. Among effective estrogen treatment patients, ERRαexpression is significantly increased, in contrast, ERRγexpression is dramatically decreased. These findings suggest that the change of ERRα/ERRγratio may be related to the development of vascular dementia and the efficacy of estrogen therapy in severe VD patients and it might be an indication for estrogen therapy. EERs will be the bio-molecular basis of the estrogen treatment in severe vascular dementia.