King Cole, Plakke Bethany
Department of Psychological Sciences, Kansas State University, 1114 Mid-Campus Drive, Manhattan, KS, 66502, USA.
Brain Behav Immun Health. 2024 Aug 3;40:100836. doi: 10.1016/j.bbih.2024.100836. eCollection 2024 Oct.
Maternal infection has long been described as a risk factor for neurodevelopmental disorders, especially autism spectrum disorders (ASD) and schizophrenia. Although many pathogens do not cross the placenta and infect the developing fetus directly, the maternal immune response to them is sufficient to alter fetal neurodevelopment, a phenomenon termed maternal immune activation (MIA). Low maternal choline is also a risk factor for neurodevelopmental disorders, and most pregnant people do not receive enough of it. In addition to its role in neurodevelopment, choline is capable of inducing anti-inflammatory signaling through a nicotinic pathway. Therefore, it was hypothesized that maternal choline supplementation would blunt the neurodevelopmental impact of MIA in offspring through long-term instigation of cholinergic anti-inflammatory signaling. To model MIA in rats, the viral mimetic polyinosinic:polycytidylic acid (poly(I:C)) was used to elicit a maternal antiviral innate immune response in dams both with and without choline supplementation. Offspring were reared to both early and late adolescent stages (postnatal days 28 and 50, respectively), where anxiety-related behaviors and cognition were examined. After behavioral testing, animals were euthanized, and their prefrontal cortices (PFCs) were collected for analysis. MIA offspring demonstrated sex-specific patterns of altered cognition and repetitive behaviors, which were modulated by maternal choline supplementation. Choline supplementation also bolstered anti-inflammatory signaling in the PFCs of MIA animals at both early and late adolescent stages. These findings suggest that maternal choline supplementation may be sufficient to blunt some of the behavioral and neurobiological impacts of inflammatory exposures , indicating that it may be a cheap, safe, and effective intervention for neurodevelopmental disorders.
长期以来，母体感染一直被认为是神经发育障碍的一个风险因素，尤其是自闭症谱系障碍（ASD）和精神分裂症。尽管许多病原体不会穿过胎盘直接感染发育中的胎儿，但母体对它们的免疫反应足以改变胎儿神经发育，这种现象被称为母体免疫激活（MIA）。母体胆碱水平低也是神经发育障碍的一个风险因素，而且大多数孕妇摄入的胆碱不足。除了在神经发育中的作用外，胆碱还能够通过烟碱途径诱导抗炎信号。因此，有人提出假设，母体补充胆碱将通过长期激发胆碱能抗炎信号来减弱MIA对后代神经发育的影响。为了在大鼠中模拟MIA，使用病毒模拟物聚肌苷酸：聚胞苷酸（poly(I:C)）在补充和未补充胆碱的母鼠中引发母体抗病毒先天免疫反应。将后代饲养到青少年早期和晚期阶段（分别为出生后第28天和第50天），检测与焦虑相关的行为和认知。行为测试后，对动物实施安乐死，并收集它们的前额叶皮质（PFC）进行分析。MIA后代表现出性别特异性的认知改变和重复行为模式，这些模式受到母体胆碱补充的调节。胆碱补充还在青少年早期和晚期阶段增强了MIA动物PFC中的抗炎信号。这些发现表明，母体补充胆碱可能足以减弱炎症暴露对行为和神经生物学的一些影响，这表明它可能是一种针对神经发育障碍的廉价、安全且有效的干预措施。
