Abstract Background: There is barely any evidence of antipsychotic drugs affecting the molecular clockwork in human, yet it is suggested that clock genes are associated with dopaminergic transmission, i.e. the main target of this therapeutics. We decided to verify if haloperidol and olanzapine affect expression of CLOCK, BMAL1, PER1 and CRY1 in a human central nervous system cell line model. Methods: U-87MG human glioblastoma cell line was used as an experimental model. The cells were incubated with or without haloperidol and olanzapine in the concentration of 5 and 20 μM for 24 h. Real-time quantitative polymerase chain reaction with the ΔCT analysis was used to examine the effect of haloperidol and olanzapine on the mRNA expression of the genes. Results: At 5 μM, haloperidol decreased expression of CRY1 almost 20-fold. There was nearly a 1.5-fold increase in expression of PER1. Considering the 20 μM haloperidol concentration and both olanzapine concentrations, no other statistically significant effect was observed. Conclusions: At certain concentration, haloperidol seems to affect expression of particular clock genes in a human central nervous system cell line model, yet mechanism underlying this phenomenon remains elusive.

中文翻译：

---

氟哌啶醇而非奥氮平可能影响人胶质母细胞瘤细胞系中PER1和CRY1基因的表达

摘要 背景：几乎没有任何证据表明抗精神病药物会影响人类分子时钟，但提示时钟基因与多巴胺能传递有关，即该疗法的主要靶点。我们决定在人类中枢神经系统细胞系模型中验证氟哌啶醇和奥氮平是否影响 CLOCK、BMAL1、PER1 和 CRY1 的表达。方法：以U-87MG人胶质母细胞瘤细胞系为实验模型。将细胞与或不与氟哌啶醇和奥氮平以 5 和 20 μM 的浓度一起孵育 24 小时。实时定量聚合酶链反应与 ΔCT 分析用于检查氟哌啶醇和奥氮平对基因 mRNA 表达的影响。结果：在 5 μM 时，氟哌啶醇使 CRY1 的表达降低了近 20 倍。几乎是1。PER1 表达增加 5 倍。考虑到 20 μM 氟哌啶醇浓度和两种奥氮平浓度，未观察到其他具有统计学意义的影响。结论：在一定浓度下，氟哌啶醇似乎会影响人类中枢神经系统细胞系模型中特定时钟基因的表达，但这种现象背后的机制仍然难以捉摸。