Maternal immune activation yields offspring displaying mouse versions of the three core symptoms of autism.
Maternal immune activation yields offspring displaying mouse versions of the three core symptoms of autism.
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DOI：
10.1016/j.bbi.2012.01.011
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发表时间：
2012-05
影响因子：
15.1
通讯作者：
Patterson, Paul H.
中科院分区：
文献类型：
--
作者：
Malkova, Natalia V.;Yu, Collin Z.;Hsiao, Elaine Y.;Moore, Marlyn J.;Patterson, Paul H.
关键词：
自闭症的核心症状是社交互动和语言缺陷，以及重复/刻板行为的存在。我们证明，与这些症状相关的行为存在于自闭症、母体感染的环境危险因素的小鼠模型中。我们通过在怀孕期间注射病毒模拟聚（I:C）来刺激母体免疫系统，并分析后代的社交和交流行为。在一项测试中，幼崽会通过超声波发声（USV）对与母亲的短暂分离做出反应。我们发现，与注射盐水的母亲所生的幼崽相比，母体免疫激活（MIA）母亲所生的幼崽在第 8 天开始的隔离测试中产生 USV 的比率较低。发声的质量也不同；对十天大幼崽的声谱图分析表明，来自 MIA 母亲的雄性幼崽发出的谐波明显较少，音节也更加复杂和短。这些沟通差异在成年后代中也很明显。与对照组相比，成年 MIA 雄性在与雌性或雄性社交接触时发出的 USV 显着减少，并且在应对雌性尿液时表现出较少的气味标记。关于第二个自闭症症状，MIA 男性表现出社交能力下降。在对自闭症特征行为的第三次测试中，MIA 后代在大理石埋葬和自我修饰测试中表现出更多的重复/刻板行为。总而言之，这些结果表明，MIA 产生的男性后代缺乏社交和交流行为，以及高度的重复行为，所有这些都是自闭症的标志。
The core symptoms of autism are deficits in social interaction and language, and the presence of repetitive/stereotyped behaviors. We demonstrate that behaviors related to these symptoms are present in a mouse model of an environmental risk factor for autism, maternal infection. We stimulate the maternal immune system by injecting the viral mimic poly(I:C) during pregnancy, and analyze the social and communicative behaviors of the offspring. In one test, young pups respond to a brief separation from the mother with ultrasonic vocalizations (USVs). We find that, compared to pups born to saline-injected mothers, pups born to maternal immune activation (MIA) mothers produce a lower rate of USVs in the isolation test starting at day 8. The quality of the vocalizations is also different; analysis of sound spectrograms of ten day-old pups shows that male pups from MIA mothers emit significantly fewer harmonic and more complex and short syllables. These communication differences are also apparent in adult offspring. Compared to controls, adult MIA males emit significantly fewer USVs in response to social encounters with females or males, and display reduced scent marking in response to female urine. Regarding a second autism symptom, MIA males display decreased sociability. In a third test of characteristic autism behaviors, MIA offspring exhibit increased repetitive/stereotyped behavior in both marble burying and self-grooming tests. In sum, these results indicate that MIA yields male offspring with deficient social and communicative behavior, as well as high levels of repetitive behaviors, all of which are hallmarks of autism.
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影响因子：
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