Vojtechova Iveta, Maleninska Kristyna, Kutna Viera, Klovrza Ondrej, Tuckova Klara, Petrasek Tomas, Stuchlik Ales
National Institute of Mental Health, Topolova 748, 25067 Klecany, Czech Republic.
Laboratory of the Neurophysiology of the Memory, Institute of Physiology of the Czech Academy of Sciences, Videnska 1083, 14220 Prague 4, Czech Republic.
Int J Mol Sci. 2021 Mar 23;22(6):3274. doi: 10.3390/ijms22063274.
Maternal immune activation (MIA) during pregnancy represents an important environmental factor in the etiology of schizophrenia and autism spectrum disorders (ASD). Our goal was to investigate the impacts of MIA on the brain and behavior of adolescent and adult offspring, as a rat model of these neurodevelopmental disorders. We injected bacterial lipopolysaccharide (LPS, 1 mg/kg) to pregnant Wistar dams from gestational day 7, every other day, up to delivery. Behavior of the offspring was examined in a comprehensive battery of tasks at postnatal days P45 and P90. Several brain parameters were analyzed at P28. The results showed that prenatal immune activation caused social and communication impairments in the adult offspring of both sexes; males were affected already in adolescence. MIA also caused prepulse inhibition deficit in females and increased the startle reaction in males. Anxiety and hypolocomotion were apparent in LPS-affected males and females. In the 28-day-old LPS offspring, we found enlargement of the brain and decreased numbers of parvalbumin-positive interneurons in the frontal cortex in both sexes. To conclude, our data indicate that sex of the offspring plays a crucial role in the development of the MIA-induced behavioral alterations, whereas changes in the brain apparent in young animals are sex-independent.
孕期母体免疫激活（MIA）是精神分裂症和自闭症谱系障碍（ASD）病因中的一个重要环境因素。作为这些神经发育障碍的大鼠模型，我们的目标是研究MIA对青少年和成年后代大脑及行为的影响。从妊娠第7天开始，每隔一天给怀孕的Wistar母鼠注射细菌脂多糖（LPS，1 mg/kg），直至分娩。在出生后第45天和第90天，通过一系列综合任务对后代的行为进行检测。在出生后第28天分析多个大脑参数。结果表明，产前免疫激活导致两性成年后代出现社交和沟通障碍；雄性在青春期就已受到影响。MIA还导致雌性前脉冲抑制缺陷，并增加雄性的惊吓反应。受LPS影响的雄性和雌性均出现焦虑和运动减少。在28日龄的LPS后代中，我们发现两性大脑均增大，额叶皮质中小清蛋白阳性中间神经元数量减少。总之，我们的数据表明，后代的性别在MIA诱导的行为改变的发展中起关键作用，而幼龄动物大脑中明显的变化与性别无关。
