Propofol Alters Long Non-Coding RNA Profiles in the Neonatal Mouse Hippocampus: Implication of Novel Mechanisms in Anesthetic-Induced Developmental Neurotoxicity.
Propofol Alters Long Non-Coding RNA Profiles in the Neonatal Mouse Hippocampus: Implication of Novel Mechanisms in Anesthetic-Induced Developmental Neurotoxicity.
复制标题
丙泊酚在新生小鼠海马中改变了长的非编码RNA谱：新机制在麻醉诱导的发育神经毒性中的影响。
DOI：
10.1159/000493875
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发表时间：
2018
期刊：
影响因子：
--
通讯作者：
Bai X
中科院分区：
文献类型：
--
作者：
Logan S;Jiang C;Yan Y;Inagaki Y;Arzua T;Bai X
异丙酚会引起急性神经毒性（例如神经细胞凋亡），进而损害动物的长期记忆和学习能力。然而，根本机制仍然很大程度上未知。研究发现长链非编码 RNA (lncRNA) 参与多种病理过程。我们假设lncRNA谱和相关信号通路发生了改变，这些变化可能与异丙酚暴露后在新生小鼠海马中观察到的神经毒性有关。在这个实验室实验中，7天大的小鼠暴露于亚麻醉剂量的异丙酚3小时，每组4只。给予异丙酚后3小时收获海马组织。使用比色测定法根据 caspase 3 活性分析神经细胞凋亡。通过微阵列研究 35,923 个 lncRNA 和 24,881 个信使 RNA (mRNA) 的概况。使用逆转录定量聚合酶链反应验证代表性差异表达的 lncRNA 和 mRNA。对所有丙泊酚失调的 mRNA 和 50 个排名前列、显着失调的 lncRNA 进行生物信息学分析，以探索丙泊酚诱导的神经毒性的潜在机制和信号网络。异丙酚诱导海马神经细胞凋亡，159个lncRNA和100个mRNA差异表达（倍数变化±2.0，P<0.05）。生物信息学分析表明，这些 lncRNA 及其相关 mRNA 可能参与神经退行性途径（例如钙处理、细胞凋亡、自噬和突触发生）。这份新颖的报告强调，异丙酚改变了 lncRNA、mRNA 及其协作信号网络的特征，这为麻醉诱导的发育性神经变性的分子机制和神经毒性的预防目标提供了新的见解。
Propofol induces acute neurotoxicity (e.g., neuroapoptosis) followed by impairment of long-term memory and learning in animals. However, underlying mechanisms remain largely unknown. Long non-coding RNAs (lncRNAs) are found to participate in various pathological processes. We hypothesized that lncRNA profile and the associated signaling pathways were altered, and these changes might be related to the neurotoxicity observed in the neonatal mouse hippocampus following propofol exposure. In this laboratory experiment, 7-day-old mice were exposed to a subanesthetic dose of propofol for 3 hours, with 4 animals per group. Hippocampal tissues were harvested 3 hours after propofol administration. Neuroapoptosis was analyzed based on caspase 3 activity using a colorimetric assay. A microarray was performed to investigate the profiles of 35,923 lncRNAs and 24,881 messenger RNAs (mRNAs). Representative differentially expressed lncRNAs and mRNAs were validated using reverse transcription quantitative polymerase chain reaction. All mRNAs dysregulated by propofol and the 50 top-ranked, significantly dysregulated lncRNAs were subject to bioinformatics analysis for exploring the potential mechanisms and signaling network of propofol-induced neurotoxicity. Propofol induced neuroapoptosis in the hippocampus, with differential expression of 159 lncRNAs and 100 mRNAs (fold change ± 2.0, P<0.05). Bioinformatics analysis demonstrated that these lncRNAs and their associated mRNAs might participate in neurodegenerative pathways (e.g., calcium handling, apoptosis, autophagy, and synaptogenesis). This novel report emphasizes that propofol alters profiles of lncRNAs, mRNAs, and their cooperative signaling network, which provides novel insights into molecular mechanisms of anesthetic-induced developmental neurodegeneration and preventive targets against the neurotoxicity.
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影响因子：
6.9
作者：
Mitchell, Amanda C.;Leak, Rehana K.;Garbett, Krassimira;Zigmond, Michael J.;Cameron, Judy L.;Mirnics, Karoly
通讯作者：
Mirnics, Karoly
影响因子：
64.8
作者：
Lin, Yingxi;Bloodgood, Brenda L.;Hauser, Jessica L.;Lapan, Ariya D.;Koon, Alex C.;Kim, Tae-Kyung;Hu, Linda S.;Malik, Athar N.;Greenberg, Michael E.
通讯作者：
Greenberg, Michael E.
产后早期使用异丙酚会抑制海马神经发生。
影响因子：
5.1
作者：
Huang, Jing;Jing, Sheng;Fan, Xiaotang
通讯作者：
Fan, Xiaotang
影响因子：
4.6
作者：
Fraguas, Susanna;Barberan, Sara;Cebria, Francesc
通讯作者：
Cebria, Francesc
影响因子：
3.7
作者：
Dholakia U;Clark-Price SC;Keating SCJ;Stern AW
通讯作者：
Stern AW