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Embryonic intraventricular exposure to autism-specific maternal autoantibodies produces alterations in autism-like stereotypical behaviors in offspring mice

机译:胚胎脑室内暴露于自闭症特异性母体自身抗体会在后代小鼠中产生自闭症样定型行为的改变

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摘要

Multiple studies have implicated a role of maternal autoantibodies reactive against fetal brain proteins specific to autism in the etiology of autism spectrum disorders (ASD). In the current study, we examined the impact of brain-reactive maternal autoantibodies of mothers of children with autism (MAU) on offspring behavior in mice compared to offspring exposed to non-reactive IgG of mothers of typically developing children (MTD). Embryonic offspring were exposed to a single intraventricular injection of MAU or MTD IgG on embryonic day 14. Offspring were allowed to mature to adulthood and were subsequently tested for sociability and stereotypic behaviors using a 3-chambered social approach task, marble burying task, and assessment of spontaneous grooming behaviors in response to a novel environment. Results indicate that MAU offspring display autistic-like stereotypic behavior in both marble burying and spontaneous grooming behaviors. Additionally, small alterations in social approach behavior were also observed in MAU offspring compared to MTD offspring. This report demonstrates for the first time the effects of a single, low dose intraventricular exposure of IgG derived from individual MAU samples on offspring behavior.
机译:多项研究表明,母体自身抗体在自闭症谱系障碍(ASD)的病因中对自闭症具有特异性的胎儿脑蛋白具有反应性。在当前的研究中,我们检查了自闭症儿童母亲的脑反应性母体自身抗体(MAU)对小鼠后代行为的影响,而后代暴露于典型发育儿童母亲的非反应性IgG后代(MTD)。在胚胎第14天,将胚胎后代单次脑室内注射MAU或MTD IgG,使后代成熟至成年,随后使用3室社交方法任务,大理石掩埋任务和评估对其社交性和定型行为进行测试对新型环境的自发修饰行为的说明。结果表明,MAU后代在大理石埋葬和自发修饰行为中均表现出自闭症式的定型行为。此外,与MTD的后代相比,MAU的后代在社交方式上的行为也有微小的改变。该报告首次证明了来自单个MAU样品的IgG的单次低剂量脑室内暴露对后代行为的影响。

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