非典型抗精神病药物目前是治疗精神分裂症的一线药物,喹硫平是该组中最常见的处方代表之一。除了它对多种受体的特异性亲和力,这种化合物具有其他生物学特性,其中抗炎作用是强烈建议。同时,发表的数据表明,炎症和小胶质细胞激活可以通过刺激CD200受体(CD200R)来减少,其通过与其配体(CD200)或可溶性CD200融合蛋白(CD200Fc)结合而发生。因此,在本研究中,我们试图评估喹硫平是否会影响小胶质细胞活性的某些方面,包括CD200-CD200R和CX3CL1-CX3CR1轴,参与神经元-小胶质细胞相互作用的调节,以及小胶质细胞促炎和抗炎谱的选定标记物的表达(Cd40,IL-1β,Il-6,Cebpb,Cd206、Arg1、Il-10和Tgf-β)。同时,我们研究了喹硫平和CD200Fc对IL-6和IL-10蛋白水平的影响.在由对照大鼠(对照OCC)或接受母体免疫激活(MIAOCC)的后代制备的器官型皮质培养物(OCC)中研究了上述方面,这是一种广泛实施的探索动物精神分裂症样紊乱的方法。实验是在基础条件下和额外暴露于细菌内毒素脂多糖(LPS)后进行的,根据精神分裂症的“两次命中”假设。我们的研究结果表明,在基础条件下,对照和MIAOCC在乳酸脱氢酶和一氧化氮释放以及Cd200r方面对LPS处理的反应存在差异。IL-1β,IL-6和Cd206表达。细菌内毒素的额外刺激导致两种类型的OCC中促炎和抗炎小胶质细胞标志物的mRNA水平显着变化。喹硫平降低了LPS对IL-1β的影响,对照OCC中的Il-6、Cebpb和Arg1表达以及MIAOCC中的IL-6和IL-10水平。此外,CD200Fc降低了细菌内毒素对MIAOCC中IL-6产生的影响。因此,我们的结果表明喹硫平,以及CD200Fc对CD200R的刺激,有益地影响LPS诱导的神经免疫变化,包括小胶质细胞相关的激活。
Atypical antipsychotics currently constitute the first-line medication for schizophrenia, with quetiapine being one of the most commonly prescribed representatives of the group. Along with its specific affinity for multiple receptors, this compound exerts other biological characteristics, among which anti-inflammatory effects are strongly suggested. Simultaneously, published data indicated that inflammation and microglial activation could be diminished by stimulation of the CD200 receptor (CD200R), which takes place by binding to its ligand (CD200) or soluble CD200 fusion protein (CD200Fc). Therefore, in the present study, we sought to evaluate whether quetiapine could affect certain aspects of microglial activity, including the CD200-CD200R and CX3CL1-CX3CR1 axes, which are involved in the regulation of neuron-microglia interactions, as well as the expression of selected markers of the pro- and anti-inflammatory profile of microglia (Cd40, Il-1β, Il-6, Cebpb, Cd206, Arg1, Il-10 and Tgf-β). Concurrently, we examined the impact of quetiapine and CD200Fc on the IL-6 and IL-10 protein levels. The abovementioned aspects were investigated in organotypic cortical cultures (OCCs) prepared from the offspring of control rats (control OCCs) or those subjected to maternal immune activation (MIA OCCs), which is a widely implemented approach to explore schizophrenia-like disturbances in animals. The experiments were performed under basal conditions and after additional exposure to the bacterial endotoxin lipopolysaccharide (LPS), according to the \"two-hit\" hypothesis of schizophrenia. The results of our research revealed differences between control and MIA OCCs under basal conditions and in response to treatment with LPS in terms of lactate dehydrogenase and nitric oxide release as well as Cd200r, Il-1β, Il-6 and Cd206 expression. The additional stimulation with the bacterial endotoxin resulted in a notable change in the mRNA levels of pro- and anti-inflammatory microglial markers in both types of OCCs. Quetiapine diminished the influence of LPS on Il-1β, Il-6, Cebpb and Arg1 expression in control OCCs as well as on IL-6 and IL-10 levels in MIA OCCs. Moreover, CD200Fc reduced the impact of the bacterial endotoxin on IL-6 production in MIA OCCs. Thus, our results demonstrated that quetiapine, as well as the stimulation of CD200R by CD200Fc, beneficially affected LPS-induced neuroimmunological changes, including microglia-related activation.