The effect of gluten in rats on cognitive functions via NMDA receptor

The impact of gluten in foods containing wheat, rye and oats, as a large part of our daily diet, on individuals without gluten intolerance and the mechanisms behind these effects are still a matter of debate today. It can be hypothesized that an immune response to gliadin, a gluten protein, may cause a cross-reaction with NMDA receptor, and affect cognitive functions due to the similarities between the protein and the amino acid sequence of the receptor. In this study, it was aimed to determine the effects of long-term diets with different levels of gluten on anxiety, locomotor activity, learning and memory functions during the developmental period and to evaluate the possible mechanisms of these effects. Male Wistar albino rats, in the infantile period, were fed standard (0.56%, n=7), gluten-free (0%, n=8) and high-gluten (12.56%, n=7) pellet feeds with the same calorie and protein content for 3 months. The open field maze was used to assess anxiety and locomotor activity changes, while the Morris water maze was used to assess learning and memory skills. The alterations in the levels of NMDA receptor in brain tissue, plasma anti-NMDAR, anti-tissue transglutaminase, anti-gliadin antibody and alpha-2-macroglobulin levels were measured using IIFT and ELISA methods. The levels of total protein, albumin and globulin in plasma were also determined by using the photometric method. Body mass index of high-gluten group was higher than that of gluten-free group (p<0.05). There was no significant difference among the diet groups in terms of brain and cerebellum weights as well as NMDA receptor levels, anxiety levels and locomotor activities (p <0.05). However, the NMDA receptor levels were negatively correlated with the time spent in the central area, an indicator of low anxiety in the open field maze (r=-0,713, p=0,004). After the training in the Morris water maze, all diet groups showed similar spatial learning performance. However, the total moving duration and the velocity of the high-gluten group were significantly higher than those of the gluten-free group (p<0.05). When the average velocity was taken as 18.20 cm/sec, it was found that the time spent finding the platform area in the gluten-free group was significantly shorter than in the high-gluten group (p=0,016). High-gluten diet did not result in an immune response against gliadin, tissue transglutaminase and NMDA receptor in rats, but total protein and globulin levels were significantly higher in high-gluten group with respect to the gluten-free group (p<0,05). In conclusion, according to our literature review, this thesis study demonstrated the effects of long-term feeding with gluten-free and the diets which have different amounts of gluten on physical development, immune response, anxiety, locomotor activity, learning and memory functions in rats from the infantile period for the first time. In addition, the relationship between the levels of brain tissue NMDA receptor and rat behavioral tests were evaluated.