Cow's milk allergy in mice is associated with neuroimmune responses in the central nervous system

Autism spectrum disorder (ASD) is multifactorial, with both genetics and environmental factors working together to develop the autistic phenotype. ASD is frequently associated with gastrointestinal dysfunction. In addition, there appear to be immunological disturbances in autistic individuals and a role of cow milk allergy has been suggested in ASD. Parental reports suggest that excluding cow's milk from the diet improves autistic behavior. Here we examined whether cow's milk allergic mice exert behavioural and neuroimmune alterations. C3H mice were orally sensitized with whey protein and cholera toxin (CT) or CT alone for 5 weeks and subsequently orally challenged with whey protein once (Fig. 1). One day after challenge, a social interaction test was performed (Fig. 2), whereupon colon and brain were obtained for cytokine and serotonin (5-HT) analysis. In the social interaction test, cow's milk allergic mice showed less social interaction (Fig. 3), while their motor activity was not affected. The concentration of 5-HT in the colon of cow's milk allergic mice showed a two fold increase compared to controls (Fig. 4). Furthermore, serotonin turnover (5-HIAA/5-HT) in the dorsal hippocampus of cow's milk allergic mice was significantly increased (Fig. 4). On cytokine level, a significant increase in IL-17, IL-1a and IL-5 was observed in whole brain homogenates. The decrease in social interaction observed in cow'smilk allergic mice might be the result of alterations in serotonin biosynthesis and degradation pathways, immune responses in the central nervous system, or a combination of both. In future studies, the role of 5-HT and cytokines in the development of disturbed social interaction will be studied as possible targets for medical nutritional concepts or pharmaceutical compounds. This study was performed within the framework of Focus en Massa Program Drug Innovation of the Utrecht University, Utrecht The Netherlands. (Figure presented) .