Ma Shuyan, Qing Li, Yang Xiaobo, Liang Guiqiang, Zhang Li'e, Li Qin, Xiong Feng, Peng Suwan, Ma Yifei, Huang Xiaowei, Zou Yunfeng
Teaching and Research Section of Hygienic Toxicology, School of Public Health, Guangxi Medical University, Nanning, Guangxi, People's Republic of China.
Department of Occupational Health and Environmental Health, School of Public Health, Guangxi Medical University, Nanning, Guangxi, People's Republic of China.
PLoS One. 2016 Jan 8;11(1):e0145856. doi: 10.1371/journal.pone.0145856. eCollection 2016.
Manganese (Mn) is an essential trace element, while excessive expose may induce neurotoxicity. Recently, lncRNAs have been extensively studied and it has been confirmed that lncRNAs participate in neural functions and aberrantly expressed lncRNAs are involved in neurological diseases. However, the pathological effects of lncRNAs on Mn-induced neurotoxicity remain unclear. In this study, the expression profiles of lncRNAs and messenger RNAs (mRNAs) were identified in Mn-treated hippocampal neurons and control neurons via microarray. Bioinformatic methods and intersection analysis were also employed. Results indicated that 566, 1161, and 1474 lncRNAs meanwhile 1848, 3228, and 4022 mRNAs were aberrantly expressed in low, intermediate, and high Mn-exposed groups compared with the control group, respectively. Go analysis determined that differentially expressed mRNAs were targeted to biological processes, cellular components, and molecular functions. Pathway analysis indicated that these mRNAs were enriched in insulin secretion, cell cycle, and DNA replication. Intersection analysis denominated that 135 lncRNAs and 373 mRNAs were consistently up-regulated while 150 lncRNAs and 560 mRNAs were consistently down-regulated. Meanwhile, lncRNA BC079195 was significantly up-regulated while lncRNAs uc.229- and BC089928 were significantly down-regulated in three comparison groups. The relative expression levels of 3 lncRNAs and 4 mRNAs were validated through qRT-PCR. To the best of our knowledge, this study is the first to identify the expression patterns of lncRNAs and mRNAs in hippocampal neurons of Sprague-Dawley rats. The results may provide evidence on underlying mechanisms of Mn-induced neurotoxicity, and aberrantly expressed lncRNAs/mRNAs may be useful in further investigations to detect early symptoms of Mn-induced neuropsychiatric disorders in the central nervous system.
锰（Mn）是一种必需的微量元素，而过度接触可能会诱发神经毒性。近年来，长链非编码RNA（lncRNAs）受到广泛研究，并且已经证实lncRNAs参与神经功能，而异常表达的lncRNAs与神经疾病有关。然而，lncRNAs对锰诱导的神经毒性的病理作用仍不清楚。在本研究中，通过微阵列鉴定了锰处理的海马神经元和对照神经元中lncRNAs和信使核糖核酸（mRNAs）的表达谱。还采用了生物信息学方法和交集分析。结果表明，与对照组相比，低、中、高锰暴露组分别有566、1161和1474个lncRNAs以及1848、3228和4022个mRNAs异常表达。基因本体（Go）分析确定差异表达的mRNAs靶向生物过程、细胞成分和分子功能。通路分析表明这些mRNAs在胰岛素分泌、细胞周期和DNA复制中富集。交集分析表明，135个lncRNAs和373个mRNAs持续上调，而150个lncRNAs和560个mRNAs持续下调。同时，lncRNA BC079195在三个比较组中显著上调，而lncRNAs uc.229 -和BC089928显著下调。通过定量逆转录聚合酶链反应（qRT-PCR）验证了3个lncRNAs和4个mRNAs的相对表达水平。据我们所知，本研究首次鉴定了Sprague-Dawley大鼠海马神经元中lncRNAs和mRNAs的表达模式。这些结果可能为锰诱导神经毒性的潜在机制提供证据，并且异常表达的lncRNAs/mRNAs可能有助于进一步研究以检测中枢神经系统中锰诱导的神经精神障碍的早期症状。
