miR-127在精神分裂症中的作用及其靶点研究
首发时间:2020-06-19
摘要:目的:研究miR-127在急性注射地卓西平(dizocilpine,MK-801)诱导的精神分裂症模型中的作用及其靶点,并探讨其可能的作用机制。方法:C57BL/6成年小鼠随机分为对照组和MK-801组,分别单次腹腔注射生理盐水和MK-801(0.4mg/kg i.p.),30 min和2 h后分别检测miR-127在前额叶皮层组织中的表达水平。体外培养原代皮层神经元,给予NMDA受体拮抗剂AP-5,利用Real-time PCR检测miR-127的表达水平。运用生物信息学软件TargetScan预测miR-127的潜在靶基因,并采用荧光素酶报告基因(luciferase)和Western blot等方法进行验证。结果:与对照组相比,MK-801处理组小鼠前额叶皮层中miR-127表达明显下调。原代皮层神经元给予AP-5处理30 min后miR-127表达下调。在前额叶皮层组织中敲低miR-127引起Synaptopodin(SYNPO)蛋白水平的上调,过表达miR-127降低SYNPO蛋白表达水平。荧光素酶报告基因活性检测显示SYNPO和miR-127有相互作用。结论:本研究发现miR-127在急性注射MK-801诱导的精神分裂模型中表达下调,并且miR-127靶向调控SYNPO基因,为后续精神分裂症的治疗提供了新的思路。
关键词: 药理学 精神分裂 miR-127 地卓西平 SYNPO
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The role of miR-127 in schizophrenia
Abstract:Objective: To explore the effects of miR-127 in acute dizocilpine(MK-801, 0.4mg/kg i.p.)-induced schizophrenia and its target. Methods: Mouse were divied into the MK-801 and control groups randomly, these groups were given intraperitoneal injection of MK-801 or saline(SAL). The expression of miR-127 in prefrontal cortex after MK-801 treatment were detected by Real-time PCR. In vitro, the expression of miR-127 were detected with NMDA receptor specific antagonist AP-5 treatment in primary cortical neuron by Real-time PCR. Using bioinformatics software TargetScan to predict the potential target genes of miR-127. Western blot and luciferase reporter assay were performed to identify the target gene of miR-127. Results: In the MK-801 groups, relative expression of miR-127 were significantly decreased at 30 min and 2 h in prefrontal cortex after MK-801 administration. In vitro, the relative expression of miR-127 were decreased at 30 min after NMDA receptor specific antagonist AP-5 treatment in primary cortical neuron. Western blot and luciferase reporter assay suggested that miR-127 directly target the 3\'un-translated region (UTR) of synaptopodin (SYNPO) mRNA to regulate the protein levels of SYNPO in prefrontal cortex, indicating that SYNPO may be the target gene of miR-127. Conclusions: These findings suggest that miR-127 are decreased in acute MK-801- induced schizophrenia and target the synaptopodin (SYNPO) gene, which provides new clues for future research of miR-127 in schizophrenia.
Keywords: Pharmacology Schizophrenia miR-127 MK-801 SYNPO
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