Activation of the maternal immune system (MIA) during gestation is linked to neuropsychiatric diseases like schizophrenia. While many studies address behavioural aspects, less is known about underlying cellular mechanisms. In the following study, BALB/c mice received intraperitoneal injections of polyinosinic-polycytidylic acid (Poly I:C) (20 µg/ml) or saline (0.9%) at gestation day (GD) 9.5 before hippocampal neurons were isolated and cultured from embryonic mice for further analysis. Interestingly, strongest effects were observed when the perineuronal net (PNN) wearing subpopulation of neurons was analysed. Here, a significant reduction of aggrecan staining intensity, area and soma size could be detected. Alterations of PNNs are often linked to neuropsychiatric diseases, changes in synaptic plasticity and in electrophysiology. Utilizing multielectrode array analysis (MEA), we observed a remarkable increase of the spontaneous network activity in neuronal networks after 21 days in vitro (DIV) when mother mice suffered a prenatal immune challenge. As PNNs are associated with GABAergic interneurons, our data indicate that this neuronal subtype might be stronger affected by a prenatal MIA. Degradation or damage of this subtype might cause the hyperexcitability observed in the whole network. In addition, embryonic neurons of the Poly I:C condition developed significantly shorter axons after five days in culture, while dendritic parameters and apoptosis rate remained unchanged. Structural analysis of synapse numbers revealed an increase of postsynaptic density 95 (PSD-95) puncta after 14 DIV and an increase of presynaptic vesicular glutamate transporter (vGlut) puncta after 21 DIV, while inhibitory synaptic proteins were not altered.

中文翻译：

---

Poly I:C 诱导的母体免疫攻击减少了神经元周围网面积并提高了体外海马神经元的自发网络活动

妊娠期间母体免疫系统 (MIA) 的激活与精神分裂症等神经精神疾病有关。虽然许多研究涉及行为方面，但对潜在的细胞机制知之甚少。在以下研究中，BALB/c 小鼠在妊娠第 9.5 天接受腹腔注射聚肌苷酸 (Poly I:C) (20 µg/ml) 或生理盐水 (0.9%)，然后分离和培养海马神经元。胚胎小鼠进行进一步分析。有趣的是，当分析佩戴神经元亚群的神经周围网 (PNN) 时，观察到了最强的影响。在这里，可以检测到蛋白聚糖染色强度、面积和体细胞大小的显着降低。PNN 的改变通常与神经精神疾病、突触可塑性和电生理学的变化有关。利用多电极阵列分析 (MEA)，我们观察到，当母鼠遭受产前免疫挑战时，在体外 (DIV) 21 天后，神经元网络中的自发网络活动显着增加。由于 PNN 与 GABA 能中间神经元相关，我们的数据表明这种神经元亚型可能受到产前 MIA 的影响更大。该亚型的退化或损伤可能导致在整个网络中观察到的过度兴奋。此外，Poly I:C 条件下的胚胎神经元在培养 5 天后显着缩短了轴突，而树突参数和细胞凋亡率保持不变。