Expression Profiles of Long Noncoding RNAs and Messenger RNAs in Mn-Exposed Hippocampal Neurons of Sprague-Dawley Rats Ascertained by Microarray: Implications for Mn-Induced Neurotoxicity

PLoS One. 2016 Jan 8;11(1):e0145856. doi: 10.1371/journal.pone.0145856. eCollection 2016.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cells, Cultured
  • Down-Regulation / drug effects*
  • Gene Regulatory Networks / drug effects
  • Hippocampus / cytology
  • Hippocampus / drug effects
  • Hippocampus / metabolism*
  • Manganese / toxicity*
  • Oligonucleotide Array Sequence Analysis
  • RNA, Long Noncoding / genetics
  • RNA, Long Noncoding / metabolism*
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism*
  • Rats
  • Rats, Sprague-Dawley
  • Real-Time Polymerase Chain Reaction
  • Toxicity Tests
  • Up-Regulation / drug effects*

Substances

  • RNA, Long Noncoding
  • RNA, Messenger
  • Manganese

Grants and funding

This work was financially supported by the National Natural Science Foundation of China (Nos. 81160339 and 21467003), China Postdoctoral Science Foundation (No. 2014M562500XB), and Guangxi Natural Science Foundation (No. 2011GXNSFA018187).