Effects of pinto bean and resistant starch supplementation on memory and cognition in estrogen-deficient mice

In the U.S., ~70% of Alzheimer’s disease (AD) cases are women. AD pathology progression and memory impairment are more severe in women, which could be triggered by estrogen loss during menopause. Three-month-old C57BL/6 female mice were injected daily with vinyl cyclohexene diepoxide (VCD), an estrogen depletion drug, or vehicle (VH) for 30 days. Mice were then randomly assigned to one of three dietary groups (n=10/group): control, 10% pinto bean (PB), and resistant starch (RS3) for 12 weeks. Behavioral tasks were then conducted, including open-field (OF) maze (a measure of anxiety/stress and exploration), Y-maze (a measure of short-term memory and exploration), and the Morris water maze (MWM) (a measure of learning ability, short/long-term memory, and cognitive function). At harvest, fecal short-chain fatty acids (SCFAs) and β-glucuronidase were quantified. The OF trials showed no differences between the VCD and VH mice. MWM 24-hour probe trials showed no differences between estrogen status nor diet. However, in the MWM 72-hour probe trials, VH mice traveled further in the annular zone than VCD mice, but differences between dietary groups are unclear. In the Y-Maze, PB-VH mice spent more time mobile than PB-VCD and Control-VH mice and traveled further in the novel arm than PB-VCD mice. Fecal SCFAs and β-glucuronidase were measured at harvest, with RS3 dietary group demonstrating significant elevation of both parameters. The PB dietary group demonstrated higher fecal SCFAs, but not β-glucuronidase. In conclusion, behavior data indicate that VCD mice overall may tend to have lower performance in long-term memory trials than VH mice, but the overall effect of diet on cognition remains unclear. Fecal data indicate that PB and/or RS3 supplementation can significantly increase SCFA and/or β-glucuronidase, which may have benefits to neuronal health. Additional work will examine differences in progressive learning ability/strategy and differences in estrogen expression in the hippocampus to better analyze the neuronal effects of estrogen status and dietary treatment.