Maternal immune activation (MIA) is a risk factor for neurodevelopmental disorders in offspring, but the pathomechanism is largely unknown. The aim of our study was to analyse the molecular mechanisms contributing to synaptic alterations in hippocampi of adolescent rats exposed prenatally to MIA. MIA was evoked in pregnant female rats by i.p. administration of lipopolysaccharide at gestation day 9.5. Hippocampi of offspring (52–53-days-old rats) were analysed using transmission electron microscopy (TEM), qPCR and Western blotting. Moreover, mitochondrial membrane potential, activity of respiratory complexes, and changes in glutathione system were measured. It was found that MIA induced changes in hippocampi morphology, especially in the ultrastructure of synapses, including synaptic mitochondria, which were accompanied by impairment of mitochondrial electron transport chain and decreased mitochondrial membrane potential. These phenomena were in agreement with increased generation of reactive oxygen species, which was evidenced by a decreased reduced/oxidised glutathione ratio and an increased level of dichlorofluorescein (DCF) oxidation. Activation of cyclin-dependent kinase 5, and phosphorylation of glycogen synthase kinase 3β on Ser9 occurred, leading to its inhibition and, accordingly, to hypophosphorylation of microtubule associated protein tau (MAPT). Abnormal phosphorylation and dysfunction of MAPT, the manager of the neuronal cytoskeleton, harmonised with changes in synaptic proteins. In conclusion, this is the first study demonstrating widespread synaptic changes in hippocampi of adolescent offspring prenatally exposed to MIA.

产妇的免疫激活（MIA）是后代神经发育障碍的危险因素，但其致病机理尚不清楚。我们研究的目的是分析促成产前暴露于MIA的青春期大鼠海马突触改变的分子机制。在妊娠第9.5天通过腹腔注射脂多糖在怀孕的雌性大鼠中诱发MIA。使用透射电子显微镜（TEM），qPCR和Western印迹分析后代（52-53日龄大鼠）的海马体。此外，还测量了线粒体膜电位，呼吸复合物的活性以及谷胱甘肽系统的变化。发现MIA诱导了海马形态的变化，尤其是突触的超微结构，包括突触线粒体的变化，伴随着线粒体电子传输链的损伤和线粒体膜电位的降低。这些现象与活性氧的产生增加是一致的，这可以通过减少/氧化的谷胱甘肽比率和增加的二氯荧光素（DCF）氧化水平来证明。细胞周期蛋白依赖性激酶5的激活和糖原合酶激酶3β在Ser9上的磷酸化，导致其抑制，并因此导致微管相关蛋白tau（MAPT）的磷酸化不足。神经元细胞骨架的管理者MAPT的异常磷酸化和功能异常与突触蛋白的变化协调一致。总之，这是第一个证明产前暴露于MIA的青春期后代海马中突触变化的广泛研究。