title: 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.
authors: Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Faculty of Science, Utrecht University, Utrecht, The Netherlands. Electronic address: c.g.m.detheije@uu.nl.
authors: Caroline G M
authors: CG
authors: de Theije
authors: Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Faculty of Science, Utrecht University, Utrecht, The Netherlands.
authors: Jiangbo
authors: J
authors: Wu
authors: Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Faculty of Science, Utrecht University, Utrecht, The Netherlands.
authors: Pim J
authors: PJ
authors: Koelink
authors: Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Faculty of Science, Utrecht University, Utrecht, The Netherlands.
authors: Gerdien A H
authors: GA
authors: Korte-Bouws
authors: Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Faculty of Science, Utrecht University, Utrecht, The Netherlands.
authors: Yuliya
authors: Y
authors: Borre
authors: Department of Translational Neuroscience, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, The Netherlands.
authors: Martien J H
authors: MJ
authors: Kas
authors: Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Faculty of Science, Utrecht University, Utrecht, The Netherlands; Nutricia Research, Utrecht, The Netherlands.
authors: Sofia
authors: S
authors: Lopes da Silva
authors: Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Faculty of Science, Utrecht University, Utrecht, The Netherlands.
authors: S Mechiel
authors: SM
authors: Korte
authors: Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Faculty of Science, Utrecht University, Utrecht, The Netherlands.
authors: Berend
authors: B
authors: Olivier
authors: Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Faculty of Science, Utrecht University, Utrecht, The Netherlands; Nutricia Research, Utrecht, The Netherlands.
authors: Johan
authors: J
authors: Garssen
authors: Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Faculty of Science, Utrecht University, Utrecht, The Netherlands.
authors: Aletta D
authors: AD
authors: Kraneveld
mesh_terms: D000367:Age Factors; D000818:Animals; D001321:Autistic Disorder / Q000209:etiology*; D015306:Biogenic Monoamines / Q000378:metabolism; D001921:Brain / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D004195:Disease Models, Animal; D005512:Food Hypersensitivity / Q000150:complications* / Q000473:pathology* / Q000523:psychology; D006120:Grooming / Q000502:physiology; D006719:Homovanillic Acid / Q000378:metabolism; D007398:Interpersonal Relations; D008297:Male; D018782:Maze Learning; D051379:Mice; D008809:Mice, Inbred C3H; D008892:Milk / Q000009:adverse effects; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D018709:Statistics, Nonparametric; D014364:Tryptophan / Q000378:metabolism
chemical_list: D015306:Biogenic Monoamines; D016760:Proto-Oncogene Proteins c-fos; D014364:Tryptophan; D006719:Homovanillic Acid
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