Protective effects of atypical antipsychotic drugs on PC12 cells after serum withdrawal
Protective effects of atypical antipsychotic drugs on PC12 cells after serum withdrawal
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DOI：
10.1002/jnr.10290
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发表时间：
2002-07-15
影响因子：
4.2
通讯作者：
Li, XM
中科院分区：
文献类型：
--
作者：
Bai, O;Wei, ZL;Li, XM
非典型抗精神病药物广泛用于精神分裂症的治疗，临床证据表明，早期和长期干预这些药物将改善长期预后。然而，目前尚不清楚非典型抗精神病药物是否也具有神经保护作用。为了澄清这一问题，我们使用 PC12 细胞培养物和细胞活力 MTT 测定来确定不同浓度的非典型抗精神病药物氯氮平、喹硫平和利培酮在血清停药后是否具有神经保护作用。此外，为了探索药物的作用，使用Northern blot检测SOD1（铜/锌超氧化物歧化酶）和p75NTR（p75神经营养蛋白受体）的基因表达。结果表明：1）抗精神病药物可以保护PC12细胞免于血清停药后死亡；这些药物处理组的细胞活力与培养基中不含血清的组有显着差异（P < 0.01）； 2) 这些药物将 SOD1 基因表达上调至 120% 以上（P < 0.05），并将 p75NTR mRNA 水平下调至各自对照值的 65% 以下（P < 0.05）。这些发现表明，非典型抗精神病药氯氮平、喹硫平和利培酮可能通过调节 SOD1 和 p75NTR 的表达发挥神经保护功能。 (C) 2002 Wiley-Liss, Inc.
Atypical antipsychotic drugs are widely used in the treatment of schizophrenia, and clinical evidence has shown that early and prolonged intervention with these drugs will improve the long-term outcome. It is still unclear, however, whether the atypical antipsychotic drugs are also neuroprotective. To clarify,this matter, we used PC12 cell cultures and the MTT assay for cell viability to determine whether various concentrations of the atypical antipsychotics clozapine, quetiapine, and risperidone are neuroprotective after serum withdrawal. In addition, to explore the drugs' actions, Northern blot was used to examine the gene expression of SOD1 (Cu/Zn superoxide dismutase) and p75NTR (p75 neurotrophin receptor). The results demonstrated that 1) the antipsychotic drugs can protect PC12 cells from death after serum withdrawal; cell viability in these drug treatment groups is significantly different from that in the groups without serum in the medium (P < 0.01); and 2) these drugs up-regulated the SOD1 gene expression to more than 120% (P < 0.05) and also down-regulated p75NTR mRNA levels to less than 65% of their respective control values (P < 0.05). These findings suggest that the atypical antipsychotics clozapine, quetiapine, and risperidone may exert a neuroprotective function through the modulation of SOD1 and p75NTR expression. (C) 2002 Wiley-Liss, Inc.