Machado Christopher J, Whitaker Alexander M, Smith Stephen E P, Patterson Paul H, Bauman Melissa D
Department of Psychiatry and Behavioral Sciences, University of California, Davis, Sacramento; California National Primate Research Center, Davis.
Division of Biology, California Institute of Technology, Pasadena.
Biol Psychiatry. 2015 May 1;77(9):823-32. doi: 10.1016/j.biopsych.2014.07.035. Epub 2014 Aug 30.
Sickness during pregnancy is associated with an increased risk of offspring neurodevelopmental disorders. Rodent models have played a critical role in establishing causal relationships and identifying mechanisms of altered brain and behavior development in pups prenatally exposed to maternal immune activation (MIA). We recently developed a novel nonhuman primate model to bridge the gap between human epidemiological studies and rodent models of prenatal immune challenge. Our initial results demonstrated that rhesus monkeys given the viral mimic synthetic double-stranded RNA (polyinosinic:polycytidylic acid stabilized with poly-l-lysine) during pregnancy produce offspring with abnormal repetitive behaviors, altered communication, and atypical social interactions.
We utilized noninvasive infrared eye tracking to further evaluate social processing capabilities in a subset of the first trimester MIA-exposed offspring (n = 4) and control animals (n = 4) from our previous study.
As juveniles, the MIA offspring differed from control animals on several measures of social attention, particularly when viewing macaque faces depicting the fear grimace facial expression. Compared with control animals, MIA offspring had a longer latency before fixating on the eyes, had fewer fixations directed at the eyes, and spent less total time fixating on the eyes of the fear grimace images.
In the rhesus monkey model, exposure to MIA at the end of the first trimester results in abnormal gaze patterns to salient social information. The use of noninvasive eye tracking extends the findings from rodent MIA models to more human-like behaviors resembling those in both autism spectrum disorder and schizophrenia.
孕期疾病与后代神经发育障碍风险增加有关。啮齿动物模型在建立因果关系以及确定产前暴露于母体免疫激活(MIA)的幼崽大脑和行为发育改变的机制方面发挥了关键作用。我们最近开发了一种新型非人灵长类动物模型,以弥合人类流行病学研究与产前免疫挑战的啮齿动物模型之间的差距。我们的初步结果表明,孕期接受病毒模拟物合成双链RNA(用聚-L-赖氨酸稳定的聚肌苷酸:聚胞苷酸)的恒河猴所产后代具有异常的重复行为、沟通改变和非典型社交互动。
我们利用非侵入性红外眼动追踪技术,对我们之前研究中孕早期暴露于MIA的一部分后代(n = 4)和对照动物(n = 4)的社交处理能力进行了进一步评估。
作为幼猴,MIA后代在几项社交注意力指标上与对照动物不同,尤其是在观看描绘恐惧鬼脸面部表情的猕猴面部时。与对照动物相比,MIA后代在注视眼睛之前的延迟时间更长,注视眼睛的次数更少,并且注视恐惧鬼脸图像眼睛的总时间更少。
在恒河猴模型中,孕早期末暴露于MIA会导致对显著社交信息的注视模式异常。非侵入性眼动追踪技术的应用将啮齿动物MIA模型的研究结果扩展到了更类似于自闭症谱系障碍和精神分裂症中人类行为的行为。