title: Dietary long chain n-3 polyunsaturated fatty acids prevent impaired social behaviour and normalize brain dopamine levels in food allergic mice.
abstract: Allergy is suggested to exacerbate impaired behaviour in children with neurodevelopmental disorders. We have previously shown that food allergy impaired social behaviour in mice. Dietary fatty acid composition may affect both the immune and nervous system. The aim of this study was to assess the effect of n-3 long chain polyunsaturated fatty acids (n-3 LCPUFA) on food allergy-induced impaired social behaviour and associated deficits in prefrontal dopamine (DA) in mice. Mice were fed either control or n-3 LCPUFA-enriched diet before and during sensitization with whey. Social behaviour, acute allergic skin response and serum immunoglobulins were assessed. Monoamine levels were measured in brain and intestine and fatty acid content in brain. N-3 LCPUFA prevented impaired social behaviour of allergic mice. Moreover, n-3 LCPUFA supplementation increased docosahexaenoic acid (DHA) incorporation into the brain and restored reduced levels of prefrontal DA and its metabolites 3,4-dihydroxyphenylacetic acid, 3-methoxytyramine and homovanillic acid in allergic mice. In addition to these brain effects, n-3 LCPUFA supplementation reduced the allergic skin response and restored decreased intestinal levels of serotonin metabolite 5-hydroxyindoleacetic acid in allergic mice. N-3 LCPUFA may have beneficial effects on food allergy-induced deficits in social behaviour, either indirectly by reducing the allergic response and restoring intestinal 5-HT signalling, or directly by DHA incorporation into neuronal membranes, affecting the DA system. Therefore, it is of interest to further investigate the relevance of food allergy-enhanced impairments in social behaviour in humans and the potential benefits of dietary n-3 LCPUFA supplementation.
authors.affiliation: Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Faculty of Science, Utrecht University, Universiteitsweg 99, 3584 CG, Utrecht, The Netherlands. Electronic address: c.g.m.detheije@uu.nl.
authors.forename: Caroline G M
authors.initials: CG
authors.lastname: de Theije
authors.affiliation: Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Faculty of Science, Utrecht University, Universiteitsweg 99, 3584 CG, Utrecht, The Netherlands.
authors.forename: Lieke W J
authors.initials: LW
authors.lastname: van den Elsen
authors.affiliation: Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Faculty of Science, Utrecht University, Universiteitsweg 99, 3584 CG, Utrecht, The Netherlands.
authors.forename: Linette E M
authors.initials: LE
authors.lastname: Willemsen
authors.affiliation: Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Faculty of Science, Utrecht University, Universiteitsweg 99, 3584 CG, Utrecht, The Netherlands.
authors.forename: Vanja
authors.initials: V
authors.lastname: Milosevic
authors.affiliation: Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Faculty of Science, Utrecht University, Universiteitsweg 99, 3584 CG, Utrecht, The Netherlands.
authors.forename: Gerdien A H
authors.initials: GA
authors.lastname: Korte-Bouws
authors.affiliation: Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Faculty of Science, Utrecht University, Universiteitsweg 99, 3584 CG, Utrecht, The Netherlands; Nutricia Research, Uppsalalaan 12, 3584 CT, Utrecht, The Netherlands.
authors.forename: Sofia
authors.initials: S
authors.lastname: Lopes da Silva
authors.affiliation: Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Faculty of Science, Utrecht University, Universiteitsweg 99, 3584 CG, Utrecht, The Netherlands; Nutricia Research, Uppsalalaan 12, 3584 CT, Utrecht, The Netherlands.
authors.forename: Laus M
authors.initials: LM
authors.lastname: Broersen
authors.affiliation: Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Faculty of Science, Utrecht University, Universiteitsweg 99, 3584 CG, Utrecht, The Netherlands.
authors.forename: S Mechiel
authors.initials: SM
authors.lastname: Korte
authors.affiliation: Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Faculty of Science, Utrecht University, Universiteitsweg 99, 3584 CG, Utrecht, The Netherlands.
authors.forename: Berend
authors.initials: B
authors.lastname: Olivier
authors.affiliation: Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Faculty of Science, Utrecht University, Universiteitsweg 99, 3584 CG, Utrecht, The Netherlands; Nutricia Research, Uppsalalaan 12, 3584 CT, Utrecht, The Netherlands.
authors.forename: Johan
authors.initials: J
authors.lastname: Garssen
authors.affiliation: Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Faculty of Science, Utrecht University, Universiteitsweg 99, 3584 CG, Utrecht, The Netherlands.
authors.forename: Aletta D
authors.initials: AD
authors.lastname: Kraneveld
mesh_terms: D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000503:physiopathology*; D053818:Chymases / Q000097:blood; D004032:Diet; D004195:Disease Models, Animal; D004281:Docosahexaenoic Acids / Q000378:metabolism; D004298:Dopamine / Q000031:analogs & derivatives / Q000378:metabolism*; D005231:Fatty Acids, Unsaturated / Q000008:administration & dosage*; D005512:Food Hypersensitivity / Q000178:diet therapy* / Q000503:physiopathology*; D006719:Homovanillic Acid / Q000378:metabolism; D006897:Hydroxyindoleacetic Acid / Q000378:metabolism; D007136:Immunoglobulins / Q000097:blood; D007413:Intestinal Mucosa / Q000378:metabolism; D008297:Male; D008809:Mice, Inbred C3H; D012701:Serotonin / Q000378:metabolism; D012879:Skin Physiological Phenomena; D012919:Social Behavior
chemical_list: D005231:Fatty Acids, Unsaturated; D007136:Immunoglobulins; D015102:3,4-Dihydroxyphenylacetic Acid; D004281:Docosahexaenoic Acids; D012701:Serotonin; D006897:Hydroxyindoleacetic Acid; D053818:Chymases; C509230:Mcpt1 protein, mouse; C001746:3-methoxytyramine; D004298:Dopamine; D006719:Homovanillic Acid
keywords: Autism spectrum disorders; Dopamine; Food allergy; Long chain n-3 polyunsaturated fatty acids; Prefrontal cortex; Serotonin; Social behaviour