(P11-37-26) Effects of Resistant Starch Supplementation on Learning and Memory in Ovariectomized Mice

Objectives: This study investigated whether supplementation with retrograded (RS3) or chemically modified (RS4) resistant starch could modulate short-chain fatty acid (SCFA) production and improve learning and memory outcomes in a mouse model of estrogen deficiency.

Methods: 3-mo-old female C57BL/6 mice were either ovariectomized (OVX) or sham-operated (Sham) and then divided into three dietary groups (n=11/group) in a 2x3 factorial design: control (AIN-93M), 5% (wt/wt) RS3 or RS4 for 12 wks. Fecal SCFAs including acetic, propionic, and n-butyric acids were assessed by GC-FID, as these metabolites are important signaling molecules in the gut-brain axis. Whole body composition which reflects metabolic status that can affect brain health was assessed using dual energy x-ray absorptiometry. Morris water maze testing (MWM) which include a 5-day training period followed by 24- and 72-h probe trials was conducted to assess short and long-term memory, and spatial learning. Behavior data were analyzed via linear mixed models and the rest with 2-way ANOVA with estrogen status (OVX/Sham) and diet as factors followed by Tukey's post-hoc tests when P < 0.05.

Results: There was a significant main effect of OVX on body composition, with OVX significantly increasing % fat (P≤0.001) while decreasing % lean (P≤0.001) mass but RS had no effect. Relative brain weight was also decreased (P≤0.001) in OVX compared to SHAM, but diet showed no significant effect on brain weight. A significant main effect of diet, but not OVX, was observed for n-butyric acid with both RS3 (P.=0.017) and RS4 (P=0.027) significantly increasing n-butyric acid compared to control. Preliminary data from MWM testing demonstrate no significant behavioral differences between OVX and Sham, nor any significant impact of diet.

Conclusions: This study provides preliminary evidence that OVX and diet did not significantly impact learning and memory outcomes in OVX mice. However, both RS3 and RS4 improves n-butyrate, a critical metabolite in the gut-brain axis. Further behavioral tests using Y-maze and open field tests are ongoing to evaluate memory and general anxiety-related behaviors.

Funding Sources: NIH-NIA/NICCH and Williams Professorship