Depletion of Dietary Bovine Milk Exosomes Impairs Sensorimotor Gating and Spatial Learning in C57BL/6 Mice

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BackgroundBovine milk exosomes contain cargos such as miRNAs, mRNAs, DNA and proteins. We have demonstrated that dietary bovine exosomes deliver functional RNA species and regulate genes and metabolism in humans and other non‐bovine species. Preliminary studies suggest that RNAs obtained through milk exosomes accumulate in the brain of mice.HypothesisDepletion of dietary bovine milk exosomes affects cognitive performance in C57BL/6 mice.MethodsC57BL/6 mice were fed AIN‐93G based, bovine milk exosome‐defined diets for up to 20 weeks. Exosome‐depleted diets are denoted E−; exosome‐sufficient controls are denoted E+. Spatial learning and memory were assessed using the Barnes maze and Morris water maze. Sensorimotor gating was assessed using an acoustic startle response (ASR) system. The statistical significance of differences was assessed by unpaired, two‐tailed t‐test.ResultsThe time needed to locate the escape hole in the Barnes maze increased by up to 130% in mice fed the E− diet compared to E+ controls (Fig. 1). Likewise, the time needed to locate and reach the submerged escape platform in the Morris water maze was significantly greater in female mice fed E− diet than female controls (Fig. 2). Prepulse inhibition (PPI) of the ASR is a measure of sensorimotor gating, and was significantly lower in female mice fed the E− diet than in female controls (Fig. 3). Diet did not affect PPI in male mice (p>0.05).Conclusion & future plansDiets defined by their content of bovine milk exosomes affect sensorimotor gating and cognitive performance in mice. Future studies will investigate which regions and cells in the brain accumulate dietary milk exosome RNA cargos, and whether a distinct species of RNA is responsible for the phenotypes reported here.Support or Funding InformationSupport: NIFA 2015‐67017‐23181, NIFA 2016‐67001‐25301/NIH DK107264, NIH 1P20GM104320, the Gerber Foundation, and USDA Hatch Act and W3002.