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食物过敏小鼠模型中的类自闭症行为和神经化学变化

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

作者信息

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

机构信息

Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Faculty of Science, Utrecht University, Utrecht, The Netherlands.

Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Faculty of Science, Utrecht University, Utrecht, The Netherlands.

出版信息

Behav Brain Res. 2014 Mar 15;261:265-74. doi: 10.1016/j.bbr.2013.12.008. Epub 2013 Dec 12.

DOI:10.1016/j.bbr.2013.12.008
PMID:24333575
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.

摘要

食物过敏被认为与心理和精神特质的表现有关,包括自闭症谱系障碍(ASD)中固有的社交行为障碍和重复行为。该领域的大多数研究很少受到关注,因为显示食物过敏免疫反应对社交行为有直接影响的基本证据非常有限。在本研究中,我们表明断奶后不久诱导的对牛奶蛋白的食物过敏反应会降低小鼠的社交行为并增加重复行为。这种食物过敏反应会增加血清素(5-羟色胺;5-HT)水平和5-HT阳性细胞数量,并降低肠道中5-羟吲哚乙酸(5-HIAA)水平。食物过敏小鼠的行为变化伴随着前额叶皮质中多巴胺能活性的降低。此外,在接触社交目标后,前额叶皮质中的神经元激活(c-Fos表达)增加,而下丘脑室旁核中的神经元激活减少。我们假设肠道过敏反应调节复杂但关键的神经免疫相互作用,从而影响参与社交互动、重复行为和认知 的脑回路。与遗传易感性和多种环境因素一起,过敏免疫激活的这些影响可能会加剧ASD患者的行为异常。

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