(OR23-04-25) Effects of Blueberry Supplementation on Markers of Cognitive Function and Behavior in UM-HET3 Mice Fed a High-Fat, High-Sucrose, High-Salt Diet

Objectives: High-fat, high-sucrose, and high-salt (HFHSS) diets are associated with cognitive decline and neuroinflammation. Blueberries (BB), rich in anthocyanins, may improve cognitive function and reduce oxidative stress. This study aims to investigate the effects of BB supplementation on cognitive function and neuroprotection in mice fed a HFHSS diet.

Methods: UM-HET3 male mice were fed a low-fat, low-sucrose, low-salt (LFLSS) diet with or without BB (5% w/w) for 4 weeks. LFLSS + BB mice were then switched to a HFHSS + BB diet (n = 9), while the rest were randomized to either remain on the LFLSS diet (n = 9), or switch to HFHSS (n = 9) for 12 weeks. Fear conditioning test was conducted during weeks 14–15 and recordings analyzed using AnyMaze (v7.48). Mice were sacrificed at weeks 16 and hippocampi were collected for protein expression analyses. Behavior data were analyzed using Two-way ANOVA while protein data was analyzed by One-Way ANOVA followed by Tukey’s posthoc test.

Results: All groups demonstrated effective learning via increased freezing behavior. During cue-dependent memory (QDM) testing, the HFHSS + BB group trended towards reduced freezing compared to LFLSS (ρ = 0.2) and HFHSS (ρ = 0.1). The HFHSS + BB group exhibited increased freezing compared to HFHSS during long-term retention (ρ = 0.01). During context-dependent memory (CDM) testing, HFHSS + BB had significantly reduced freezing (ρ = 0.02) compared to HFHSS. Glial Fibrillary Acidic Protein (Gfap) expression was numerically increased in the HFHSS group (ρ = 0.3) compared to LFLSS but tended to be attenuated by BB supplementation (p = 0.08). Expression of Neuronal Nuclei (NeuN), a marker associated with neuron maturity, was lower in the HFHSS + BB group compared to both HFHSS (p = 0.07) and LFLSS (p = 0.08) groups. No effect was observed on the expression of brain-derived neurotrophic factor and the serotonin receptor 5-HT1A among groups.

Conclusions: Our findings indicate that BB supplementation may have neuroprotective effects and enhance long-term memory retention (QDM) while also reducing context-associated fear responses (CDM), suggesting potential for dietary interventions to improve memory specificity. Further studies of larger sample size are warranted.

Funding Sources: Lewis College Foundation Award