Gene Expression Of Methylation Cycle And Related Genes In Lymphocytes And Brain Of Patients With Schizophrenia And Non-Psychotic Controls.
Gene Expression Of Methylation Cycle And Related Genes In Lymphocytes And Brain Of Patients With Schizophrenia And Non-Psychotic Controls.
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DOI：
10.1016/j.bionps.2021.100038
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发表时间：
2021-12-01
影响因子：
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通讯作者：
Smith, Robert C
中科院分区：
文献类型：
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作者：
Sershen, Henry;Guidotti, Alessandro;Smith, Robert C
精神分裂症潜在的一些生化异常涉及甲基化和甲基化酶以及其他相关靶基因的差异。我们目前的研究结果在外周血淋巴细胞（PBL）和死后的慢性精神分裂症（CSZ）和非精神病对照（NPC）的大脑mRNA表达的差异，强调性别和抗精神病药物治疗的mRNA结果的差异影响。我们研究了61例CSZ和49例NPC受试者淋巴细胞中的mRNA表达，使用TaqMan探针进行qPCR分析，以评估DNMT、泰特、GABA能、NR 3C 1、BDNF mRNA以及最近RNA序列分析中鉴定的几种其他靶点的水平。同时，我们对19例CSZ和26例NPC脑组织中的DNMT 1和GAD 67进行了研究。在PBLs中，DNMT 1和DNMT 3A mRNA水平在男性CSZ中显著高于NPC。在雌性动物中未检测到显著差异。GAD 1、NR 3C 1和CNTNAP 2 mRNA在CSZ中的表达均显著高于NPC。在接受氯氮平治疗的CSZ患者中，GAD-1相关、CNTNAP 2和IMPA 2 mRNA显著高于未接受氯氮平治疗的CSZ受试者。CSZ与NPC之间这些mRNA的差异主要归因于氯氮平治疗。在脑组织样本中，CSZ组DNMT 1显著高于NPC组，GAD 67显著低于NPC组，但诊断效果无显著性别差异。这些发现强调了在评估CSZ和NPC之间mRNA差异的实质性意义时考虑性别和药物治疗效果的重要性。
Some of the biochemical abnormalities underlying schizophrenia, involve differences in methylation and methylating enzymes, as well as other related target genes. We present results of a study of differences in mRNA expression in peripheral blood lymphocytes (PBLs) and post-mortem brains of chronic schizophrenics (CSZ) and non-psychotic controls (NPC), emphasizing the differential effects of sex and antipsychotic drug treatment on mRNA findings. We studied mRNA expression in lymphocytes of 61 CSZ and 49 NPC subjects using qPCR assays with TaqMan probes to assess levels of DNMT, TET, GABAergic, NR3C1, BDNF mRNAs, and several additional targets identified in a recent RNA sequence analysis. In parallel we studied DNMT1 and GAD67 in samples of brain tissues from 19 CSZ, 26 NPC. In PBLs DNMT1 and DNMT3A mRNA levels were significantly higher in male CSZ vs NPC. No significant differences were detected in females. The GAD1, NR3C1 and CNTNAP2 mRNA levels were significantly higher in CSZ than NPC. In CSZ patients treated with clozapine, GAD-1 related, CNTNAP2, and IMPA2 mRNAs were significantly higher than in CSZ subjects not treated with clozapine. Differences between CSZ vs NPC in these mRNAs was primarily attributable to the clozapine treatment. In the brain samples, DNMT1 was significantly higher and GAD67 was significantly lower in CSZ than in NPC, but there were no significant sex differences in diagnostic effects. These findings highlight the importance of considering sex and drug treatment effects in assessing the substantive significance of differences in mRNAs between CSZ and NPC.