de Theije Caroline G M, van den Elsen Lieke W J, Willemsen Linette E M, Milosevic Vanja, Korte-Bouws Gerdien A H, Lopes da Silva Sofia, Broersen Laus M, Korte S Mechiel, Olivier Berend, Garssen Johan, Kraneveld Aletta D
Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Faculty of Science, Utrecht University, Universiteitsweg 99, 3584 CG, Utrecht, The Netherlands.
Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Faculty of Science, Utrecht University, Universiteitsweg 99, 3584 CG, Utrecht, The Netherlands.
Neuropharmacology. 2015 Mar;90:15-22. doi: 10.1016/j.neuropharm.2014.11.001. Epub 2014 Nov 12.
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.
过敏被认为会加剧神经发育障碍儿童的行为受损。我们之前已经表明食物过敏会损害小鼠的社交行为。饮食中的脂肪酸组成可能会影响免疫系统和神经系统。本研究的目的是评估n-3长链多不饱和脂肪酸（n-3 LCPUFA）对食物过敏诱导的小鼠社交行为受损以及前额叶多巴胺（DA）相关缺陷的影响。在用乳清致敏之前和期间，给小鼠喂食对照饮食或富含n-3 LCPUFA的饮食。评估社交行为、急性过敏性皮肤反应和血清免疫球蛋白。测量大脑和肠道中的单胺水平以及大脑中的脂肪酸含量。n-3 LCPUFA可预防过敏小鼠的社交行为受损。此外，补充n-3 LCPUFA可增加二十二碳六烯酸（DHA）在大脑中的掺入，并恢复过敏小鼠前额叶DA及其代谢产物3,4-二羟基苯乙酸、3-甲氧基酪胺和高香草酸降低的水平。除了这些大脑效应外，补充n-3 LCPUFA还可降低过敏小鼠的过敏性皮肤反应，并恢复其肠道中血清素代谢产物5-羟吲哚乙酸降低的水平。n-3 LCPUFA可能通过减少过敏反应和恢复肠道5-羟色胺信号间接对食物过敏诱导的社交行为缺陷产生有益影响，或者通过DHA掺入神经元膜直接影响DA系统。因此，进一步研究食物过敏增强的人类社交行为损伤的相关性以及饮食中补充n-3 LCPUFA的潜在益处是很有意义的。
