Autistic-like behavioural and neurochemical changes in a mouse model of food allergy

Abstract

Food allergy has been suggested to contribute to the expression of psychological and psychiatric traits, including disturbed social behaviour and repetitive behaviour inherent in autism spectrum disorders (ASD). Most research in this field receives little attention, since fundamental evidence showing direct effects of food allergic immune responses on social behaviour is very limited. In the present study, we show that a food allergic reaction to cow's milk protein, induced shortly after weaning, reduced social behaviour and increased repetitive behaviour in mice. This food allergic reaction increased levels of serotonin (5-hydroxytryptamine; 5-HT) and the number of 5-HT positive cells, and decreased levels of 5-hydroxyindoleacetic acid (5-HIAA) in the intestine. Behavioural changes in food allergic mice were accompanied by reduced dopaminergic activity in the prefrontal cortex. Furthermore, neuronal activation (c-Fos expression) was increased in the prefrontal cortex and reduced in the paraventricular nucleus of the hypothalamus after exposure to a social target. We hypothesize that an intestinal allergic response regulates complex, but critical, neuroimmune interactions, thereby affecting brain circuits involved in social interaction, repetitive behaviour and cognition. Together with a genetic predisposition and multiple environmental factors, these effects of allergic immune activation may exacerbate behavioural abnormalities in patients with ASD.

Keywords: 3,4-dihydroxyphenylacetic acid; 3-MT; 3-methoxytyramine; 5-HIAA; 5-HT; 5-hydroxyindoleacetic acid; ASD; Autism spectrum disorders; DA; DOPAC; DSS; EC; Food allergy; HVA; Ig; Monoamines; Neuronal activation; PVN; Repetitive behaviour; SERT; Social behaviour; TRP; autism spectrum disorders; dextran sodium sulphate; dopamine; enterochromaffin cell; homovanillic acid; hypothalamic paraventricular nucleus; immunoglobulin; l-tryptophan; mMCP-1; mouse mast cell protease-1; oPFC; orbital prefrontal cortex; serotonin; serotonin transporter.