Background and Aim. MK801-induced psychotic symptoms and also the Ras homolog family member A (RhoA) expression and cell division control protein 42 (cdc42) mRNA modulation in the rat brain have been investigated. Antipsychotic drugs (APDs) have been reported to induce Rho GDP-dissociation inhibitor (RhoGDI) pathway regulation related to cytoskeleton reorganization in neuronal cells. It will be necessary to clarify the effects of APDs on MK801-induced RhoGDI signaling regulation in neuronal cells. Methods. B35 neuronal cells were treated with MK801 for 7 days then treated with MK801 in combination with haloperidol or clozapine for a further 7 days. Cell migration, F-actin condensation, and RhoGDI signaling regulation were examined to investigate the regulatory effects of MK801, haloperidol, and clozapine in B35 neuronal cells. Results. MK801 reduced B35 cell migration, whereas both haloperidol and clozapine reversed the reduction in cell migration induced by MK801. Haloperidol and clozapine restored F-actin condensation after it was diminished by MK801 in B35 cell nuclei. MK801 increased the RhoGDI1 and RhoA expression, which was diminished by the addition of haloperidol and clozapine. MK801 reduced the CDC42 expression, which was restored by haloperidol and clozapine. MK801 reduced the Rho-associated coiled-coil containing protein kinase 1 (ROCK1), profilin1 (PFN1), and neuronal Wiskott–Aldrich Syndrome protein (N-WASP) expression, which was further reduced by haloperidol and clozapine. MK801 also increased the phosphorylated myosin light chain 2 (p-MLC2), postsynaptic density protein 95 (PSD-95), and c-jun expression, which was decreased by haloperidol and clozapine. p21 (RAC1-) activated kinase 1 (PAK1) expression was not affected by MK801.

中文翻译：

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抗精神病药物通过调节B35细胞中Rho信号通路逆转MK801抑制的细胞迁移和F-肌动蛋白凝集。

背景和目的。已经研究了MK801引起的精神病症状以及大鼠脑中Ras同源家族成员A（RhoA）表达和细胞分裂控制蛋白42（cdc42）mRNA的调节。据报道，抗精神病药物（APDs）诱导与神经元细胞中细胞骨架重组有关的Rho GDP分离抑制剂（RhoGDI）途径调节。有必要澄清APD对神经元细胞中MK801诱导的RhoGDI信号传导调节的影响。方法。B35神经元细胞用MK801处理7天，然后用MK801与氟哌啶醇或氯氮平联用再处理7天。检查了细胞迁移，F-肌动蛋白缩合和RhoGDI信号调节，以研究MK801，氟哌啶醇和氯氮平对B35神经元细胞的调节作用。结果。MK801减少了B35细胞迁移，而氟哌啶醇和氯氮平均逆转了MK801诱导的细胞迁移减少。氟哌啶醇和氯氮平通过B35细胞核中的MK801减少了F-肌动蛋白的凝结。MK801增加了RhoGDI1和RhoA的表达，但由于加入了氟哌啶醇和氯氮平而使其表达降低。MK801降低了CDC42表达，氟哌啶醇和氯氮平可恢复该表达。MK801降低了Rho相关的卷曲螺旋蛋白激酶1（ROCK1），脯氨酸蛋白1（PFN1）和神经元Wiskott-Aldrich综合征蛋白（N-WASP）的表达，氟哌啶醇和氯氮平进一步降低了该表达。MK801还增加了磷酸化的肌球蛋白轻链2（p-MLC2），突触后密度蛋白95（PSD-95）和c-jun表达，氟哌啶醇和氯氮平可降低这些表达。