Expression Signature of lncRNAs and mRNAs in Sevoflurane-Induced Mouse Brain Injury: Implication of Involvement of Wide Molecular Networks and Pathways.
Expression Signature of lncRNAs and mRNAs in Sevoflurane-Induced Mouse Brain Injury: Implication of Involvement of Wide Molecular Networks and Pathways.
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DOI：
10.3390/ijms22031389
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发表时间：
2021-01-30
影响因子：
5.6
通讯作者：
Bai X
中科院分区：
文献类型：
--
作者：
Jiang C;Arzua T;Yan Y;Bai X
七氟醚是最常用的儿科麻醉剂之一，被发现会导致发育神经毒性。为了了解特定的风险群体并制定对策，需要更好地了解其机制。我们假设，与许多其他脑退化途径一样，长非编码 RNA (lncRNA) 参与了七氟醚诱导的神经毒性。出生后第 7 天 (PD7) 小鼠暴露于 3% 七氟醚 6 小时。为了量化这些小鼠的神经毒性，我们（1）通过分析 caspase 3 表达水平和活性检测神经细胞凋亡，（2）通过 PD60 的 Morris 水迷宫评估长期学习能力。为了阐明具体机制，使用微阵列分析对小鼠海马中的 27,427 个 lncRNA 和 18,855 个信使 RNA (mRNA) 进行了分析。通过生物信息学分析预测七氟烷诱导的异常lncRNA和mRNA表达相关功能途径。我们发现七氟醚会诱导显着的神经毒性，导致小鼠海马中PD7上的急性神经细胞凋亡以及148个mRNA和301个lncRNA的异常表达。此外，暴露的小鼠表现出对 PD60 的记忆受损。生物信息学分析预测，失调的 mRNA 与其共表达失调的 lncRNA 高度相关，可能参与 34 条神经退行性信号通路（例如脑细胞凋亡和智力发育障碍）。我们的研究首次揭示新生儿暴露于 3% 七氟醚会诱导异常的 lncRNA 和 mRNA 表达谱。这些失调的 lncRNA/mRNA 形成广泛的分子网络，可能导致海马体中的各种功能性神经疾病途径，导致观察到的急性细胞凋亡和长期记忆受损。
Sevoflurane, one of the most commonly used pediatric anesthetics, was found to cause developmental neurotoxicity. To understand specific risk groups and develop countermeasures, a better understanding of its mechanisms is needed. We hypothesize that, as in many other brain degeneration pathways, long non-coding RNAs (lncRNAs) are involved in the sevoflurane-induced neurotoxicity. Postnatal day 7 (PD7) mice were exposed to 3% sevoflurane for 6 h. To quantify neurotoxicity in these mice, we (1) detected neural apoptosis through analysis of caspase 3 expression level and activity and (2) assessed long-term learning ability via the Morris water maze at PD60. To elucidate specific mechanisms, profiles of 27,427 lncRNAs and 18,855 messenger RNAs (mRNAs) in mouse hippocampi were analyzed using microarray assays. Sevoflurane-induced abnormal lncRNA and mRNA expression-associated function pathways were predicted by bioinformatic analysis. We found that sevoflurane induced significant neurotoxicity, causing acute neuroapoptosis and abnormal expression of 148 mRNAs and 301 lncRNAs on PD7 in mouse hippocampus. Additionally, exposed mice exhibited impaired memory on PD60. Bioinformatic analysis predicted that the dysregulated mRNAs, which are highly correlated with their co-expressed dysregulated lncRNAs, might be involved in 34 neurodegenerative signaling pathways (e.g., brain cell apoptosis and intellectual developmental disorder). Our study reveals for the first time that neonatal exposure to 3% sevoflurane induces abnormal lncRNA and mRNA expression profiles. These dysregulated lncRNAs/mRNAs form wide molecular networks that might contribute to various functional neurological disease pathways in the hippocampus, resulting in the observed acute apoptosis and impaired long-term memory.
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影响因子：
--
作者：
De Hert S;Moerman A
通讯作者：
Moerman A
DOI：
10.1016/j.jtcvs.2016.03.095
发表时间：
2016-08
期刊：
The Journal of thoracic and cardiovascular surgery
影响因子：
--
作者：
Diaz LK;Gaynor JW;Koh SJ;Ittenbach RF;Gerdes M;Bernbaum JC;Zackai EH;Clancy RR;Rehman MA;Pennington JW;Burnham N;Spray TL;Nicolson SC
通讯作者：
Nicolson SC
影响因子：
12.3
作者：
Marchese FP;Raimondi I;Huarte M
通讯作者：
Huarte M
影响因子：
1.7
作者：
Lu, Guolin;Xu, Huali;Xu, Shiyuan
通讯作者：
Xu, Shiyuan
影响因子：
9.8
作者：
Hudson, A. E.;Hemmings, H. C., Jr.
通讯作者：
Hemmings, H. C., Jr.