Haddad Faraj L, Lu Lu, Baines Kelly J, Schmid Susanne
Anatomy & Cell Biology, Schulich School of Medicine & Dentistry, The University of Western Ontario, Canada.
Department of Neurology, West China Hospital of Sichuan University, Chengdu, China.
Brain Behav Immun Health. 2020 Oct 8;9:100156. doi: 10.1016/j.bbih.2020.100156. eCollection 2020 Dec.
Maternal immune activation (MIA) in response to infection during pregnancy has been linked through various epidemiological and preclinical studies to an increased risk of neurodevelopmental disorders such as autism spectrum disorder (ASD) and schizophrenia in exposed offspring. Sensory filtering disruptions occur in both of these disorders and are typically measured using the acoustic startle response in both humans and rodents. Our study focuses on characterizing the baseline reactivity, habituation and prepulse inhibition (PPI) of the acoustic startle response following exposure to MIA. We induced MIA using polyinosinic: polycytidylic acid (poly I:C) at gestational day (GD) 9.5 or 14.5, and we tested sensory filtering phenotypes in adolescent and adult offspring. Our results show that startle reactivity was robustly increased in adult GD9.5 but not GD14.5 poly I:C offspring. In contrast to some previous studies, we found no consistent changes in short-term habituation, long-term habituation or prepulse inhibition of startle. Our study highlights the importance of MIA exposure timing and discusses sensory filtering phenotypes as they relate to ASD, schizophrenia and the poly I:C MIA model. Moreover, we analyze and discuss the potential impact of between- and within-litter variability on behavioural findings in poly I:C studies.
孕期感染引发的母体免疫激活(MIA),经多项流行病学和临床前研究证实,与暴露后代患神经发育障碍(如自闭症谱系障碍(ASD)和精神分裂症)的风险增加有关。这两种疾病均存在感觉过滤障碍,通常通过人类和啮齿动物的听觉惊吓反应来测量。我们的研究重点是描述暴露于MIA后听觉惊吓反应的基线反应性、习惯化和前脉冲抑制(PPI)。我们在妊娠第9.5天或14.5天使用聚肌苷酸:聚胞苷酸(poly I:C)诱导MIA,并在青少年和成年后代中测试感觉过滤表型。我们的结果表明,成年期的妊娠第9.5天而非第14.5天接受poly I:C处理的后代,其惊吓反应性显著增加。与之前的一些研究不同,我们发现短期习惯化、长期习惯化或惊吓的前脉冲抑制没有一致的变化。我们的研究强调了MIA暴露时间的重要性,并讨论了与ASD、精神分裂症和poly I:C MIA模型相关的感觉过滤表型。此外,我们分析并讨论了窝间和窝内变异性对poly I:C研究中行为结果的潜在影响。