1681-P: Estrogen Modulates Obesity Effects on Neurobehavioral Phenotypes in a Female Mouse Model of Alzheimer’s Disease

Abstract

Introduction and Objective: Alzheimer’s disease disproportionately affects women, in particular post-menopausal women. Obesity and other molecular factors may play a role in its pathogenesis. Methods: We examined the neurobehavioral effects of diet-induced obesity and estrogen in female 5xFAD mice as a model of neurodegeneration associated with Alzheimer’s disease. Female 5xFAD mice at 12 weeks of age received ovariectomy (OVX; n=6) or sham operation (controls; n=6). An additional cohort of OVX mice received chronic estrogen replacement via osmotic pumps (10-100 ug/kg/day) (OVX+E2; n=6). Results: After 6 weeks of high-fat diet (HFD), OVX mice gained more weight than controls with a 9.0±2.1g increase over baseline compared to a 3.1±0.5g increase for controls. OVX+E2 group gained a 6.8±0.7g increase in body weight. Blood glucose levels increased by 36% from baseline in OVX group and 9% in OVX+E2 group compared to 8% in controls. We performed a novel object recognition test and found a 10% decrease in discrimination rate for OVX group compared to controls (Figure). In contrast, OVX+E2 group showed a 4% increase from OVX in discrimination rate (Figure). Conclusion: These results show that a loss of estrogen reduced neurobehavioral phenotypes, which were partially restored by estrogen replacement. Our findings suggest that estrogen may play a protective role against declining neurobehavioral phenotypes in Alzheimer's disease. Disclosure: H. Choi: None. A. Daryanani: None. J. Bowman: None. W. Martenis: None. M. Sajid: None. J. Goicolea Egia: None. M. Barbini: None. P.G. Gomez: None. L.A. Tauer: None. D. Schafer: None. J.K. Kim: None. Funding: National Institutes of Health (R01-AG085308, R01-DK133772)