Weir Ruth K, Forghany Reihaneh, Smith Stephen E P, Patterson Paul H, McAllister A Kimberly, Schumann Cynthia M, Bauman Melissa D
The Department of Psychiatry & Behavioral Sciences, University of California, Davis, CA 95817, USA; MIND Institute, University of California, Davis, CA 95817, USA.
The Department of Psychiatry & Behavioral Sciences, University of California, Davis, CA 95817, USA; MIND Institute, University of California, Davis, CA 95817, USA.
Brain Behav Immun. 2015 Aug;48:139-46. doi: 10.1016/j.bbi.2015.03.009. Epub 2015 Mar 24.
Maternal infection during pregnancy increases the risk for neurodevelopmental disorders in offspring. Rodent models have played a critical role in establishing maternal immune activation (MIA) as a causal factor for altered brain and behavioral development in offspring. We recently extended these findings to a species more closely related to humans by demonstrating that rhesus monkeys (Macaca mulatta) prenatally exposed to MIA also develop abnormal behaviors. Here, for the first time, we present initial evidence of underlying brain pathology in this novel nonhuman primate MIA model. Pregnant rhesus monkeys were injected with a modified form of the viral mimic polyI:C (poly ICLC) or saline at the end of the first trimester. Brain tissue was collected from the offspring at 3.5 years and blocks of dorsolateral prefrontal cortex (BA46) were used to analyze neuronal dendritic morphology and spine density using the Golgi-Cox impregnation method. For each case, 10 layer III pyramidal cells were traced in their entirety, including all apical, oblique and basal dendrites, and their spines. We further analyzed somal size and apical dendrite trunk morphology in 30 cells per case over a 30 μm section located 100±10 μm from the soma. Compared to controls, apical dendrites of MIA-treated offspring were smaller in diameter and exhibited a greater number of oblique dendrites. These data provide the first evidence that prenatal exposure to MIA alters dendritic morphology in a nonhuman primate MIA model, which may have profound implications for revealing the underlying neuropathology of neurodevelopmental disorders related to maternal infection.
孕期母体感染会增加后代患神经发育障碍的风险。啮齿动物模型在确立母体免疫激活（MIA）作为后代大脑和行为发育改变的因果因素方面发挥了关键作用。我们最近通过证明产前暴露于MIA的恒河猴（猕猴）也会出现异常行为，将这些发现扩展到了与人类关系更密切的物种。在此，我们首次展示了这种新型非人灵长类MIA模型中潜在脑病理学的初步证据。在妊娠早期结束时，给怀孕的恒河猴注射改良形式的病毒模拟物聚肌胞苷酸（聚肌胞苷酸，poly ICLC）或生理盐水。在后代3.5岁时收集脑组织，使用高尔基-考克斯浸染法，用背外侧前额叶皮质（BA46）块分析神经元树突形态和棘密度。对于每个病例，完整追踪10个III层锥体细胞，包括所有顶树突、斜树突和基底树突及其棘。我们进一步在距胞体100±10μm的30μm切片上，对每个病例的30个细胞分析胞体大小和顶树突主干形态。与对照组相比，MIA处理后代的顶树突直径较小，斜树突数量较多。这些数据首次证明，产前暴露于MIA会改变非人灵长类MIA模型中的树突形态，这可能对揭示与母体感染相关的神经发育障碍的潜在神经病理学具有深远意义。
