Effect of the LncRNA-LIN-miRNA-9-DRD2 regulatory network on the development of the neuronal system after inhalation of the anesthetic sevoflurane.

IF 1.7 4区 医学 Q4 NEUROSCIENCES Experimental Brain Research Pub Date : 2024-11-29 DOI:10.1007/s00221-024-06960-2
Xi'an Bao, Huajun Zhang
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Abstract

Animal studies have shown that exposure of newborns to general anesthesia drugs can lead to neurodegenerative diseases and subsequent decline in learning and memory abilities. The neurotoxicity of general anesthesia drugs can also occur in the fetus. Therefore, in order to investigate the effect of the Long non-coding RNA(LncRNA)-LIN-microRNA(miRNA)-9-Dopamine receptor D2(DRD2) regulatory network on the development of the neuronal system after the inhalation of the anesthetic sevoflurane, RT-qPCR was used to detect the mRNA levels of LncRNA-LIN, miRNA-9, and DRD2. A dual-luciferase reporter system was used to detect the relationship between LncRNA-LIN and miRNA-9, and miRNA-9 and DRD2. Western blotting and immunofluorescence staining was employed to detect the protein levels of DRD2 and cleaved caspase-3. Flow cytometry was carried out to detect the number of apoptotic cells. The escape latency, swimming distance, and platform crossing times were analyzed using the Morris water maze. The results showed that, after treatment with sevoflurane, the mRNA levels of LncRNA-LIN and DRD2, the expression levels of the DRD2 protein, and the number of neuronal levels of DRD2 were significantly decreased, whereas the expression levels of miRNA-9 and the cleaved caspase-3 protein and neuronal apoptosis were significantly increased. miR-9 knockdown revealed that miRNA-9 regulated DRD2 expression and affected the function of mouse neuronal cells. In turn, LncRNA-LIN overexpression indicated that LncRNA-LIN regulated miR-9 and affected the function of mouse neuronal cells. The present results demonstrated that the LncRNA-LIN-miRNA-9-DRD2 regulatory network is involved in the effects of the inhalation anesthetic sevoflurane on neuronal system development.

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LncRNA-LIN-miRNA-9-DRD2调控网络对吸入麻醉剂七氟醚后神经元系统发育的影响
动物研究表明,新生儿暴露于全身麻醉药物可导致神经退行性疾病和随后的学习和记忆能力下降。全身麻醉药物的神经毒性也可发生在胎儿身上。因此,为了研究长链非编码RNA(LncRNA)-LIN-microRNA(miRNA)-9-多巴胺受体D2(DRD2)调控网络对吸入麻醉剂七氟醚后神经元系统发育的影响,我们采用RT-qPCR检测LncRNA- lin、miRNA-9和DRD2的mRNA水平。采用双荧光素酶报告系统检测LncRNA-LIN与miRNA-9、miRNA-9与DRD2的关系。Western blotting和免疫荧光染色检测DRD2和cleaved caspase-3蛋白水平。流式细胞术检测凋亡细胞数。采用Morris水迷宫分析小鼠的逃跑潜伏期、游泳距离和穿越平台次数。结果显示,七氟醚处理后,LncRNA-LIN和DRD2 mRNA水平、DRD2蛋白表达水平和DRD2神经元水平均显著降低,而miRNA-9和cleaved caspase-3蛋白表达水平和神经元凋亡水平均显著升高。miR-9敲低揭示miRNA-9调控DRD2表达,影响小鼠神经元细胞功能。LncRNA-LIN过表达表明LncRNA-LIN调控miR-9,影响小鼠神经元细胞功能。本研究结果表明,LncRNA-LIN-miRNA-9-DRD2调控网络参与了吸入麻醉剂七氟醚对神经系统发育的影响。
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来源期刊
CiteScore
3.60
自引率
5.00%
发文量
228
审稿时长
1 months
期刊介绍: Founded in 1966, Experimental Brain Research publishes original contributions on many aspects of experimental research of the central and peripheral nervous system. The focus is on molecular, physiology, behavior, neurochemistry, developmental, cellular and molecular neurobiology, and experimental pathology relevant to general problems of cerebral function. The journal publishes original papers, reviews, and mini-reviews.
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