Neuroscience Graduate Program, The Ohio State University, Columbus, OH, USA.
Department of Psychology, The Ohio State University, Columbus, OH, USA.
Brain Behav Immun. 2021 Jul;95:269-286. doi: 10.1016/j.bbi.2021.03.025. Epub 2021 Mar 30.
Maternal systemic inflammation increases risk for neurodevelopmental disorders like autism, ADHD, and schizophrenia in offspring. Notably, these disorders are male-biased. Studies have implicated immune system dysfunction in the etiology of these disorders, and rodent models of maternal immune activation provide useful tools to examine mechanisms of sex-dependent effects on brain development, immunity, and behavior. Here, we employed an allergen-induced model of maternal inflammation in rats to characterize levels of mast cells and microglia in the perinatal period in male and female offspring, as well as social, emotional, and cognitive behaviors throughout the lifespan. Adult female rats were sensitized to ovalbumin (OVA), bred, and challenged intranasally on gestational day 15 of pregnancy with OVA or saline. Allergic inflammation upregulated microglia in the fetal brain, increased mast cell number in the hippocampus on the day of birth, and conferred region-, time- and sex- specific changes in microglia measures. Additionally, offspring of OVA-exposed mothers subsequently exhibited abnormal social behavior, hyperlocomotion, and reduced cognitive flexibility. These data demonstrate the long-term effects of maternal allergic challenge on offspring development and provide a basis for understanding neurodevelopmental disorders linked to maternal systemic inflammation in humans.
母体全身性炎症会增加后代患自闭症、多动症和精神分裂症等神经发育障碍的风险。值得注意的是，这些疾病存在性别偏向。研究表明，免疫系统功能障碍与这些疾病的病因有关，而母体免疫激活的啮齿动物模型为研究性别依赖性对大脑发育、免疫和行为的影响机制提供了有用的工具。在这里，我们采用过敏原诱导的母体炎症模型，在雄性和雌性后代的围产期内研究肥大细胞和小胶质细胞的水平，以及整个生命周期内的社交、情绪和认知行为。成年雌性大鼠接受卵清蛋白（OVA）致敏，繁殖，并在妊娠第 15 天经鼻内接受 OVA 或盐水挑战。过敏炎症使胎儿大脑中的小胶质细胞增多，出生当天增加海马中的肥大细胞数量，并导致小胶质细胞测量的区域、时间和性别特异性变化。此外，暴露于 OVA 的母亲的后代随后表现出异常的社交行为、过度活跃和认知灵活性降低。这些数据表明母体过敏挑战对后代发育的长期影响，并为理解与人类系统性母体炎症相关的神经发育障碍提供了基础。
