Department of Anatomy, Physiology, and Pharmacology, University of Saskatchewan, Saskatoon, SK S7N 5E5, Canada.
eNeuro. 2019 Apr 19;6(2). doi: 10.1523/ENEURO.0437-18.2019. eCollection 2019 Mar-Apr.
Sex differences are documented in psychiatric and neurological disorders, yet most preclinical animal research has been conducted in males only. There is a need to better understand of the nature of sex differences in brain disease in order to meet the needs of psychiatric patients. We present the behavior profile of adult female offspring produced using a maternal immune activation (MIA) model where pregnant rats receive an immune stimulant and the offspring typically show various abnormalities consistent with psychiatric illnesses such as schizophrenia and autism. The results in female offspring were compared to a previously published cohort of their male siblings (Lins et al., 2018). We examined prepulse inhibition (PPI), sociability, MK-801-induced locomotor activity, crossmodal object recognition (CMOR), and oddity discrimination; behaviors relevant to the positive, negative, and cognitive symptoms of schizophrenia. No between-treatment differences in PPI or locomotor activity were noted. Tactile memory was observed in the control and treated female offspring, visual recognition memory was deficient in the polyinosinic:polycytidylic acid (polyI:C) offspring only, and both groups lacked crossmodal recognition. PolyI:C offspring were impaired in oddity preference and had reduced preference for a stranger conspecific in a sociability assay. Systemic maternal CXCL1, IL-6, and TNF-a levels 3 h after polyI:C treatment were determined, but no relationship was found between these cytokines and the behavior seen in the adult female offspring. Overall, female offspring of polyI:C-treated dams display an array of behavior abnormalities relevant to psychiatric illnesses such as schizophrenia similar to those previously reported in male rats.
性别差异在精神和神经疾病中已有记载，但大多数临床前动物研究仅在雄性动物中进行。为了满足精神疾病患者的需求，有必要更好地了解大脑疾病中性别差异的本质。我们展示了使用母体免疫激活 (MIA) 模型产生的成年雌性后代的行为特征，其中怀孕的老鼠接受免疫刺激，后代通常表现出各种与精神疾病（如精神分裂症和自闭症）一致的异常。将雌性后代的结果与之前发表的雄性同胞队列（Lins 等人，2018 年）进行了比较。我们检查了预脉冲抑制（PPI）、社交性、MK-801 诱导的运动活性、跨模态物体识别（CMOR）和异常辨别；这些行为与精神分裂症的阳性、阴性和认知症状相关。在 PPI 或运动活性方面未观察到治疗之间的差异。在对照组和处理组的雌性后代中观察到触觉记忆，只有 polyI:C 后代缺乏视觉识别记忆，而两组均缺乏跨模态识别。polyI:C 后代在异常偏好方面存在障碍，在社交性测定中对陌生同种动物的偏好减少。在 polyI:C 处理后 3 小时测定了母体 CXCL1、IL-6 和 TNF-a 的系统水平，但未发现这些细胞因子与成年雌性后代的行为之间存在关系。总体而言，polyI:C 处理的母鼠的雌性后代表现出一系列与精神分裂症等精神疾病相关的行为异常，与之前在雄性大鼠中报道的异常相似。
