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

• Published in: Behavioural brain research Vol. 261; pp. 265 - 274
• Main Authors: de Theije, Caroline G.M., Wu, Jiangbo, Koelink, Pim J., Korte-Bouws, Gerdien A.H., Borre, Yuliya, Kas, Martien J.H., Lopes da Silva, Sofia, Korte, S. Mechiel, Olivier, Berend, Garssen, Johan, Kraneveld, Aletta D.
• Format: Journal Article
• Language: English
• Published: Shannon Elsevier B.V 15-03-2014; Elsevier
• Subjects: Age Factors; Animals; Autism spectrum disorders; Autistic Disorder - etiology; Biogenic Monoamines - metabolism; Biological and medical sciences; Brain - metabolism; Child clinical studies; Chromatography, High Pressure Liquid; Developmental disorders; Disease Models, Animal; Food allergy; Food Hypersensitivity - complications; Food Hypersensitivity - pathology; Food Hypersensitivity - psychology; Fundamental and applied biological sciences. Psychology; Grooming - physiology; Homovanillic Acid - metabolism; Infantile autism; Interpersonal Relations; Male; Maze Learning; Medical sciences; Mice; Mice, Inbred C3H; Milk - adverse effects; Monoamines; Neuronal activation; Proto-Oncogene Proteins c-fos - metabolism; Psychology. Psychoanalysis. Psychiatry; Psychopathology. Psychiatry; Repetitive behaviour; Social behaviour; Statistics, Nonparametric; Tryptophan - metabolism; Vertebrates: nervous system and sense organs; Food allergy; DOPAC; DSS; PVN; mMCP-1; oPFC; Monoamines; Neuronal activation; Autism spectrum disorders; ASD; HVA; SERT; TRP; Repetitive behaviour; 5-HIAA; 3-MT; Social behaviour; 5-HT; DA; EC; Ig; Immunopathology; Allergy; Animal model; Rodentia; Behavior change; Monoamine; Developmental disorder; Activation; Autism; Vertebrata; Mammalia; Social behavior; Mouse; Animal; 3,4-dihydroxyphenylacetic acid; homovanillic acid; mouse mast cell protease-1; serotonin; dextran sodium sulphate; 3-methoxytyramine; immunoglobulin; l-tryptophan; orbital prefrontal cortex; hypothalamic paraventricular nucleus; 5-hydroxyindoleacetic acid; enterochromaffin cell; serotonin transporter; dopamine
• ISSN: 0166-4328; 1872-7549
• DOI: 10.1016/j.bbr.2013.12.008

•Food allergy in mice reduced social behaviour, increased repetitive behaviour and impaired spatial memory.•Abnormalities of the serotonergic system in the intestines occurred.•c-Fos expression increased in obitofrontal cortex and decreased hypothalamic paraventricular nucleus.•Dopaminergic system was dampened in prefrontal cortex and enhanced in amygdala.
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.