Effects of Reproductive Experience on Cognitive-Behavioral Outcomes in Mouse Models of Alzheimer's Disease and Related Dementias

Effects of Reproductive Experience on Cognitive-Behavioral Outcomes in Mouse Models of Alzheimer's Disease and Related Dementias

Alvin Sherman Library

Dementias, including Alzheimer’s disease and vascular dementia, are devastating conditions lacking safe and effective treatments. Despite the striking sex/gender difference in the prevalence of dementia, few studies have investigated sex-specific factors that may influence the greater risk and faster progression of disease in females. These factors include but are not limited to prior pregnancy and motherhood. Women with children have slower rates of cognitive decline and lower risk for developing mild cognitive impairment or dementia than women with no children. However, other studies have reported mixed results, suggesting that the influence of reproductive/maternal experience may depend on an individual’s number of children and/or their geographical location. Therefore, controlled studies in animal models are needed to determine causality and mechanisms driving this relationship. We are investigating the impact of prior reproductive experience on cognitive-behavioral outcomes at around 8 or 12 months of age in wild-type controls and two transgenic mouse models of Alzheimer’s disease and related dementias, 3xTg-AD mice (exhibiting beta-amyloid and tau pathology) and Tg-SwDI mice (exhibiting parenchymal and cerebrovascular beta-amyloid accumulation). Behavioral tests include the Barnes maze, open field, elevated zero maze, novel object recognition test, object placement test, and Ymaze to assess general activity levels, anxiety-like behavior, and various aspects of learning and memory. Preliminary data suggests that prior reproductive experience may attenuate some cognitive-behavioral deficits seen in Tg-SwDI mice, and similar results are expected in 3xTg-AD mice. Our goal is to provide further insight into how maternal experience influences hippocampal function and plasticity in aging and disease.