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Gender-Dependent Effects of Maternal Immune Activation on the Behavior of Mouse Offspring

机译:母体免疫激活对小鼠后代行为的性别依赖性影响

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摘要

Autism spectrum disorders are neurodevelopmental disorders characterized by two core symptoms; impaired social interactions and communication, and ritualistic or repetitive behaviors. Both epidemiological and biochemical evidence suggests that a subpopulation of autistics may be linked to immune perturbations that occurred during fetal development. These findings have given rise to an animal model, called the “maternal immune activation” model, whereby the offspring from female rodents who were subjected to an immune stimulus during early or mid-pregnancy are studied. Here, C57BL/6 mouse dams were treated mid-gestation with saline, lipopolysaccharide (LPS) to mimic a bacterial infection, or polyinosinic:polycytidylic acid (Poly IC) to mimic a viral infection. Autism-associated behaviors were examined in the adult offspring of the treated dams. Behavioral tests were conducted to assess motor activity, exploration in a novel environment, sociability, and repetitive behaviors, and data analyses were carried independently on male and female mice. We observed a main treatment effect whereby male offspring from Poly IC-treated dams showed reduced motor activity. In the marble burying test of repetitive behavior, male offspring but not female offspring from both LPS and Poly IC-treated mothers showed increased marble burying. Our findings indicate that offspring from mothers subjected to immune stimulation during gestation show a gender-specific increase in stereotyped repetitive behavior.
机译:自闭症谱系障碍是神经发育障碍,其特征是两个核心症状。社交互动和沟通受损,以及礼节性或重复性行为受损。流行病学和生化证据均表明,自闭症亚群可能与胎儿发育期间发生的免疫扰动有关。这些发现引起了一种动物模型,称为“母体免疫激活”模型,在该模型中,研究了在怀孕早期或中期受到免疫刺激的雌性啮齿动物的后代。在这里,C57BL / 6小鼠大坝在妊娠中期用生理盐水,脂多糖(LPS)模仿细菌感染,或用多肌苷:聚胞苷酸(Poly IC)模仿病毒感染。在处理过的水坝的成年后代中检查与自闭症相关的行为。进行了行为测试以评估运动活动,在新环境中的探索,社交能力和重复行为,并且分别对雄性和雌性小鼠进行数据分析。我们观察到一种主要的治疗效果,即经过Poly IC处理的水坝的雄性后代表现出降低的运动能力。在重复性行为的大理石埋葬测试中,LPS和经Poly IC处理的母亲的雄性后代(而非雌性后代)均显示大理石埋葬增加。我们的发现表明,在妊娠期间受到免疫刺激的母亲的后代表现出性别刻板印象的重复性行为特异性增加。

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  • 总页数 9
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