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

Alzheimer's disease and vascular dementia are devastating conditions lacking safe and effective treatments. Despite the striking sex difference in dementia's prevalence, few studies have investigated sex-specific factors that likely influence the greater risk and faster progression of disease in females: prior pregnancy and motherhood. Women with children experience slower rates of cognitive decline and lower risk of developing cognitive impairment than women with no children. However, other studies report mixed results, suggesting that the influence of reproductive experience could 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 have investigated the impact of prior reproductive experience on cognitive-behavioral outcomes at 8 to 12 months of age in wild-type controls and two transgenic mouse models of AD and related dementias: 3xTg-AD mice (exhibiting beta-amyloid and tau pathology) and Tg-SwDI mice (exhibiting parenchymal and cerebrovascular beta-amyloid accumulation). A panel of behavior tests were conducted to assess general activity levels, anxiety like behavior, and learning and memory. The open field data revealed that reproductive experience increased anxiety-like behavior in 3xTg-AD, Tg-SWDI, and wild-type mice but normalized activity levels and exploratory behavior in Tg-SwDI and wild-type mice. Additionally, the Barnes maze data revealed that reproductive experience improved spatial memory in all three groups of mice. These results suggest that motherhood might confer protection against cognitive decline, warranting further investigation into the sex-specific neurobiological mechanisms mitigating AD risk and progression in women.