DNA Methylation Profiling in a Neuroblastoma Cell Line Exposed to the Antipsychotic Perospirone
DNA Methylation Profiling in a Neuroblastoma Cell Line Exposed to the Antipsychotic Perospirone
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DOI：
10.1055/s-0044-101467
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发表时间：
2019-02-01
影响因子：
4.3
通讯作者：
Iwamoto, Kazuya
中科院分区：
文献类型：
--
作者：
Murata, Yui;Bundo, Miki;Iwamoto, Kazuya
简介 越来越多的证据表明抗精神病药物引起的大脑表观遗传变化的重要性。然而，由于缺乏系统研究，它们对表观遗传状态的影响仍不清楚。在研究抗精神病药物的表观遗传效应的过程中，我们重点关注了哌罗螺隆，一种主要在日本使用的非典型抗精神病药物。方法从暴露于2种不同剂量的哌罗螺隆的人神经母细胞瘤细胞中获得基因组DNA。使用 Infinium HumanMmethylation450 BeadChip 进行全面的 DNA 甲基化分析。结果 在约 470,000 个探针中，哌罗螺酮暴露改变了 4098 个探针的 DNA 甲基化。这些探针富含神经发育基因。显示高甲基化的探针主要位于基因体和基因间区域，而显示低甲基化的探针位于启动子区域附近。此外，在多巴胺受体 2 和血清素受体 (HTR) 2A 和 HTR1A 的探针中发现了 DNA 甲基化变化，它们是非典型抗精神病药物的药理靶标。讨论我们全面的 DNA 甲基化分析将有助于更好地了解哌罗螺隆的详细药理作用。
Introduction Accumulating evidence suggests the importance of epigenetic changes in the brain induced by antipsychotic drugs. However, due to the lack of systematic investigation, their effects on epigenetic status remain largely unclear. During the course of examining the epigenetic effects of antipsychotics, we here focused on perospirone, an atypical antipsychotic drug mainly used in Japan.Methods Genomic DNA was obtained from human neuroblastoma cells exposed to 2 different doses of perospirone. Comprehensive DNA methylation analysis was performed using the Infinium HumanMethylation450 BeadChip.Results Of about 470,000 probes, perospirone exposure changed DNA methylation at 4098 probes. These probes were enriched to genes for neural development. Probes showing hypermethylation were mainly found at gene body and intergenic regions, whereas those that showed hypomethylation were located near promoter regions. Additionally, DNA methylation changes were found in the probes for dopamine receptor 2 and serotonin receptor (HTR) 2A and HTR1A, which are the pharmacological targets of atypical antipsychotics.Discussion Our comprehensive DNA methylation analyses will contribute to a better understanding of detailed pharmacological actions of perospirone.