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The interplay between prenatal exposure to valproic acid and food allergy in the behavioural and allergic response of mice and the effects of a specific multi-nutrient diet -A preliminary study-

de Theije, CG;Silva, SL;Korte, SM;Olivier, B;Garssen, J;Kraneveld, AD;

Autism spectrum disorder (ASD) is a cluster of neurodevelopmental disorders suggested to be caused by genetic predisposition in combination with environmental factors. Gastrointestinal and immune dysfunction in patients with ASD are repeatedly reported and suggested to contribute to disease progression. In the present study, we investigated the interplay between impaired neurodevelopment, induced by in utero valproic acid (VPA) exposure, and food allergy in mice as well as the effects of a multi-nutrient diet, containing specific anti-inflammatory and neuroprotective ingredients. Pregnant BALB/c females, fed either the control or the active diet, were treated subcutaneously with 500 mg/kg VPA or PBS on gestational day 11. Male offspring were sensitized with whey protein for 5 weeks. The morning after challenge with whey, social and anxiety-like behaviour were assessed and serum was collected. In this pilot study we demonstrate that social and anxiety-like behaviour in VPA exposed mice was not further impaired when a food allergic reaction was induced. However, mice exposed to VPA in utero have a distinct immunological response to allergic sensitization, characterized by reduced serum levels of antigen-specific Th1-type IgG2a. Moreover, the specific multi-nutrient diet prevented diminished IgG2a levels in VPA-exposed allergic mice. This finding adds to the hypothesis that immune dysfunction is associated with ASD and this model may open a new window for opportunities to investigate the underlying mechanism of immune dysfunction in neurodevelopmental disorders.