标题：Paliperidone protects SK-N-SH cells against glutamate toxicity via Akt1/GSK3 beta signaling pathway
作者：Peng, Lei; Zhang, Xingzhen; Cui, Xianping; Zhu, Dexiao; Wu, Jintao; Sun, Dong; Yue, Qingwei; Li, Zeyan; Liu, Haili; Li, Guibao; Zh 更多 作者机构：[Peng, Lei; Zhang, Xingzhen; Zhu, Dexiao; Wu, Jintao; Yue, Qingwei; Li, Zeyan; Liu, Haili; Li, Guibao; Zhang, Jing; Sun, Jinhao] Shandong Univ, Dept A 更多
通讯作者地址：[Sun, JH]Shandong Univ, Dept Anat, Jinan 250012, Shandong, Peoples R China.
关键词：Paliperidone; Protection; Schizophrenia; SK-N-SH; Glutamate
摘要：Schizophrenia is a heterogeneous psychotic illness and its etiology remains poorly understood. Recent studies have suggested that neurodegeneration is a component of schizophrenia pathology and some atypical antipsychotics appear to slow progressive morphological brain changes. In addition, the atypical antipsychotics were reported to have a superior therapeutic efficacy in treating schizophrenia and have a low incidence of extrapyramidal side effects (EPS) compared to typical antipsychotics. However, the mechanisms of atypical antipsychotics in treating schizophrenia and the basis for differences in their clinical effects were still totally unknown. In the present study, we investigated whether paliperidone shows protective effects on SK-N-SH cells from cell toxicity induced by exposure to glutamate. We examined the effects of the drugs on cell viability (measured by MTT metabolism assay and lactate dehydrogenase (LDH) activity assay), apoptosis rate, ROS levels and gene expression and phosphorylation of Akt1 and GSK3 beta. The results showed that paliperidone significantly increases the cell viability by MTT and LDH assays (p < 0.05), in contrast to the typical antipsychotic (haloperidol), which had little neuroprotective activity. Moreover, paliperidone retarded the glutamate-mediated promotion of ROS and the rate of apoptosis (p < 0.05). In addition, paliperidone also effectively reversed glutamate-induced decreases of gene expression and phosphorylation of Akt1 and GSK3 beta (both p < 0.05). Our results demonstrated that paliperidone could effectively protect SK-N-SH cells from glutamate-induced damages via Akt1/GSK3 beta signaling pathway. (C) 2014 Elsevier B.V. All rights reserved.