在小鼠中,由母体免疫激活引起的神经免疫和行为变化通过早期的产后免疫刺激得到改善
Lourdes K Davis1, Louise M Ince2, Sriya Gullapalli2
1Division of Pharmacology & Toxicology, College of Pharmacy, University of Texas at Austin, Austin, TX 78712, USA; Interdisciplinary Neuroscience Program, University of Texas at Austin, Austin, TX 78712, USA.
Brain, behavior, and immunity
|March 13, 2025
概括
孕产妇免疫激活 (MIA) 增加了自闭症风险,但第二次炎症打击并没有使小鼠的行为变化恶化. 单独MIA改变了免疫细胞分布和微质细胞活动,显示时间是发育病理学的关键.
科学领域:
- 神经科学是一个神经科学.
- 免疫学 免疫学 免疫学
- 发展生物学 发展生物学
背景情况:
- 自闭症谱系障碍 (ASD) 的病因是复杂的,涉及遗传和环境因素,如生命早期的炎症.
- 孕产妇免疫激活 (MIA) 与ASD发病率的增加有关,但并非所有暴露后代都会患上ASD,这表明MIA可能是病理的主要原因.
研究的目的:
- 为了测试MIA是否与二次炎症侵袭相结合时,作为ASD类病理的疾病原始剂.
- 研究MIA和随后的炎症挑战对小鼠行为和免疫结果的影响.
主要方法:
- 使用了一种两次成功的小鼠模型:母在怀孕期间接受了多酸-多酸 (Poly(I:C)) (MIA),后代的一个子组在产后接受了脂多糖 (LPS).
- 后代的行为 (社交性,重复性行为,焦虑) 在成年时被评估.
- 使用流细胞计和其他方法分析了免疫细胞群 (外周和大脑) 和微质细胞活动.
主要成果:
- 单独MIA增加了雄性小鼠的重复性行为,并在两性中减少了社交能力.
- 第二次LPS挑战并没有加剧MIA诱导的行为变化.
- 在男性中,MIA改变了CD8+T细胞的分布 (在胸腺上升,在脏,淋巴,大脑下降) 和特定区域的微质活动,而LPS可以改善这种情况.
结论:
- MIA可以诱导与ASD相关的特定行为和免疫变化,但这些不一定会因随后的炎症性侮辱而恶化.
- 炎症性压力因素的时间和性质是神经发育病态发展的关键因素.
- 这项研究强调了产前炎症和产后环境在塑造后代神经发育中的复杂相互作用.
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