Impact of clozapine on the expression of miR-675-3p in plasma exosomes derived from patients with schizophrenia
Impact of clozapine on the expression of miR-675-3p in plasma exosomes derived from patients with schizophrenia
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DOI：
10.1080/15622975.2022.2104924
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发表时间：
2022-07
期刊：
影响因子：
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通讯作者：
Yu Funahashi;Yuta Yoshino;Jun‐ichi Iga;S. Ueno
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文献类型：
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作者：
Yu Funahashi;Yuta Yoshino;Jun‐ichi Iga;S. Ueno
摘要目的近年来，有研究报道了精神分裂症（SCZ）患者血清exosomes（EXO）中microRNA（miRNAs）的表达变化。本研究旨在探讨难治性精神分裂症（TRS）患者血浆EXO中miRNA表达的整体变化及氯氮平对其表达的影响。方法采用基因芯片技术研究TRS患者和对照组血浆EXO中miRNA表达的变化。然后，用定量qPCR实验证实TRS、非TRS和对照之间的miRNA表达。我们还研究了体外SH-SY 5 Y细胞中EXO miRNA表达的变化。结果基于基因本体论分析，用于miRNA表达分析的微阵列（9个对照组与9个TRS患者）揭示了13个上调和18个下调的miRNA，其与神经元和脑发育相关。其中，上调的miR-675- 3 p表达在同一队列中通过qPCR实验成功验证。相反，miR-675- 3 p表达水平在非TRS队列中显著降低（50名对照组vs. 50名无TRS且无氯氮平治疗的患者）。结论我们发现SCZ患者血浆EXO中存在与神经功能相关的整体miRNA变化，其中hsa-miR-675- 3 p表达在氯氮平治疗后上调。
Abstract Objectives Recently, the expression changes of microRNAs (miRNAs) in the serum exosomes (EXO) of schizophrenia (SCZ) have been reported. The aim of this study was to investigate the global expression changes of miRNA derived from the plasma EXO of patients with treatment-resistant schizophrenia (TRS) and the effects of clozapine on miRNA expression. Methods Global miRNA expression changes in plasma EXO between TRS and controls were studied using microarray analysis. Then, miRNA expressions among TRS, non-TRS, and controls were confirmed with quantitative qPCR experiments. We also studied changes in EXO miRNA expression with in-vitro SH-SY5Y cells. Results A microarray for miRNA expression analysis (nine controls vs. nine patients with TRS) revealed 13 up- and 18 downregulated miRNAs that were relevant to neuronal and brain development based on gene ontology analysis. Of those, upregulated miR-675-3p expression was successfully validated in the same cohort by qPCR experiments. Conversely, miR-675-3p expression levels were significantly decreased in the non-TRS cohort (50 controls vs. 50 patients without TRS without clozapine treatment). Conclusions We identified global miRNA changes in plasma EXO derived from patients with SCZ that were relevant to neuronal functions, among which, hsa-miR-675-3p expression was upregulated by clozapine treatment.