Program in Neuroscience and Behavior, Department of Psychology and Education, Mount Holyoke College, 50 College Street, South Hadley, MA 01075, USA.
Program in Neuroscience and Behavior, Department of Psychology and Education, Mount Holyoke College, 50 College Street, South Hadley, MA 01075, USA.
J Neuroimmunol. 2024 May 15;390:578341. doi: 10.1016/j.jneuroim.2024.578341. Epub 2024 Apr 8.
Maternal allergic asthma (MAA) during pregnancy has been associated with increased risk of neurodevelopmental disorders in humans, and rodent studies have demonstrated that inducing a T helper-2-mediated allergic response during pregnancy leads to an offspring behavioral phenotype characterized by decreased social interaction and increased stereotypies. The interleukin (IL)-4 cytokine is hypothesized to mediate the neurobehavioral impact of MAA on offspring. Utilizing IL-4 knockout mice, this study assessed whether MAA without IL-4 signaling would still impart behavioral deficits. C57 and IL-4 knockout female mice were sensitized to ovalbumin, exposed to repeated MAA inductions, and their offspring performed social, cognitive, and motor tasks. Only C57 offspring of MAA dams displayed social and cognitive deficits, while IL-4 knockout mice showed altered motor activity compared with C57 mice. These findings highlight a key role for IL-4 signaling in MAA-induced behavioral deficits and more broadly in normal brain development.
母体过敏性哮喘 (MAA) 与人类神经发育障碍的风险增加有关,啮齿动物研究表明,在怀孕期间诱导辅助性 T 细胞 2 介导的过敏反应会导致后代出现行为表型,表现为社交互动减少和刻板行为增加。白细胞介素 (IL)-4 细胞因子被假设介导 MAA 对后代的神经行为影响。本研究利用 IL-4 敲除小鼠评估了没有 IL-4 信号的 MAA 是否仍会导致行为缺陷。C57 和 IL-4 敲除雌性小鼠对卵清蛋白致敏,暴露于反复的 MAA 诱导下,其后代进行社交、认知和运动任务。只有 MAA 母鼠的 C57 后代表现出社交和认知缺陷,而 IL-4 敲除小鼠与 C57 小鼠相比表现出运动活动改变。这些发现强调了 IL-4 信号在 MAA 诱导的行为缺陷中的关键作用,更广泛地说,在正常大脑发育中也具有关键作用。