Department of Molecular Psychiatry, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo, 113-8655, Japan.
Department of Neuropsychiatry, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo, 113-8655, Japan.
Pharmacopsychiatry. 2019 Feb;52(2):63-69. doi: 10.1055/s-0044-101467. Epub 2018 Feb 27.
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.
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.
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.
Our comprehensive DNA methylation analyses will contribute to a better understanding of detailed pharmacological actions of perospirone.
越来越多的证据表明，抗精神病药物在大脑中引起的表观遗传变化很重要。然而，由于缺乏系统的研究，它们对表观遗传状态的影响在很大程度上仍不清楚。在研究抗精神病药物的表观遗传效应的过程中，我们在此重点关注哌罗匹隆，一种主要在日本使用的非典型抗精神病药物。
将人类神经母细胞瘤细胞暴露于两种不同剂量的哌罗匹隆中，提取基因组 DNA。使用 Infinium HumanMethylation450 BeadChip 进行全面的 DNA 甲基化分析。
在大约 470,000 个探针中，哌罗匹隆暴露导致 4098 个探针的 DNA 甲基化发生变化。这些探针富集到神经发育相关基因。表现出过度甲基化的探针主要位于基因体和基因间区域，而表现出低甲基化的探针则位于启动子区域附近。此外，多巴胺受体 2 和血清素受体（HTR）2A 和 HTR1A 的探针也发现了 DNA 甲基化变化，它们是非典型抗精神病药物的药理学靶点。
我们全面的 DNA 甲基化分析将有助于更好地理解哌罗匹隆的详细药理学作用。
