Effect of Long-Term Ovariectomy on ER? (estrogen receptor beta)-mediated Memory Enhancement and ER? Expression in Mouse Hippocampus
Mentor 1
Karyn Frick
Location
Union Wisconsin Room
Start Date
27-4-2018 1:00 PM
Description
Although animal and clinical studies suggest estrogen therapy can benefit cognitive function in aging females, the Women’s Health Initiative Memory Study (WHIMS) suggested that estrogen therapy did not benefit cognitive functioning in post-menopausal women over age 65. Because women in the WHIMS were past the onset of menopause, it was thought that estrogen therapy was administered too late to be beneficial. This idea, the “critical period hypothesis”, posits that estrogen therapy only benefits cognition when initiated during or near the onset of menopause. Although the mechanisms underlying the critical period are unclear, they may involve alterations in estrogen receptor expression. Our laboratory has shown that infusion of 17β-estradiol into the hippocampus of ovariectomized female mice increases spatial memory consolidation in an object placement task. The beneficial effects of 17β-estradiol are mediated through various types of estrogen receptors (ER), such as ERβ. In this study, we tested the effectiveness of the ERβ agonist diarylpropionitrile (DPN) on spatial memory consolidation in mice experiencing estrogen deprivation. Female mice were ovariectomized and tested in an object placement task either one or four months after surgery. When tested one-month post-surgery, DPN-treated mice showed enhanced object placement memory. However, when tested four-months post-surgery, DPN-treated mice did not exhibit enhanced memory. These results support the critical period hypothesis suggesting DPN only enhances memory shortly after estrogen deprivation. Dorsal hippocampal tissue was collected two or five months after surgery, and levels of ERβ protein were measured using Western blotting. Relative to vehicle-treated mice, ERβ levels were significantly lower in mice treated with estradiol starting four-months after surgery. In contrast, ERβ levels did not differ between mice receiving vehicle or estradiol one-month post-surgery. Together, these findings suggest decreased ERβ levels might contribute to closing of the critical period and account for estrogen therapy’s reduced efficacy in older post-menopausal women.
Effect of Long-Term Ovariectomy on ER? (estrogen receptor beta)-mediated Memory Enhancement and ER? Expression in Mouse Hippocampus
Union Wisconsin Room
Although animal and clinical studies suggest estrogen therapy can benefit cognitive function in aging females, the Women’s Health Initiative Memory Study (WHIMS) suggested that estrogen therapy did not benefit cognitive functioning in post-menopausal women over age 65. Because women in the WHIMS were past the onset of menopause, it was thought that estrogen therapy was administered too late to be beneficial. This idea, the “critical period hypothesis”, posits that estrogen therapy only benefits cognition when initiated during or near the onset of menopause. Although the mechanisms underlying the critical period are unclear, they may involve alterations in estrogen receptor expression. Our laboratory has shown that infusion of 17β-estradiol into the hippocampus of ovariectomized female mice increases spatial memory consolidation in an object placement task. The beneficial effects of 17β-estradiol are mediated through various types of estrogen receptors (ER), such as ERβ. In this study, we tested the effectiveness of the ERβ agonist diarylpropionitrile (DPN) on spatial memory consolidation in mice experiencing estrogen deprivation. Female mice were ovariectomized and tested in an object placement task either one or four months after surgery. When tested one-month post-surgery, DPN-treated mice showed enhanced object placement memory. However, when tested four-months post-surgery, DPN-treated mice did not exhibit enhanced memory. These results support the critical period hypothesis suggesting DPN only enhances memory shortly after estrogen deprivation. Dorsal hippocampal tissue was collected two or five months after surgery, and levels of ERβ protein were measured using Western blotting. Relative to vehicle-treated mice, ERβ levels were significantly lower in mice treated with estradiol starting four-months after surgery. In contrast, ERβ levels did not differ between mice receiving vehicle or estradiol one-month post-surgery. Together, these findings suggest decreased ERβ levels might contribute to closing of the critical period and account for estrogen therapy’s reduced efficacy in older post-menopausal women.
