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Transcriptome-Wide Identification of Differentially Expressed Genes and Long Non-coding RNAs in Aluminum-Treated Rat Hippocampus

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Abstract

Aluminum (Al) is an environmental neurotoxicant with a wide exposure, but the molecular mechanism underlying its toxicity remains unclear. We used RNA sequencing (RNA-seq) in the hippocampus of Al-treated rats to identify 96 upregulated and 652 downregulated mRNAs, and 37 dysregulated long non-coding (lnc)RNAs. Gene ontology analysis showed that dysregulated genes were involved in glial cell differentiation, neural transmission, and vesicle trafficking. Kyoto Encyclopedia of Genes and Genomes pathway analysis revealed clustering of differentially expressed mRNAs and lncRNA target genes in several pathways, including the “adenosine monophosphate-activated protein kinase signaling pathway,” “extracellular matrix receptor interaction,” “the phosphatidylinositol 3 kinase–protein kinase B signaling pathway,” and “focal adhesion” signaling pathway. RNA-seq results were validated by reverse transcription (RT)-PCR. Additionally, Al induced changes to the number and morphology of glial cells in the hippocampus of rats, as shown by glial fibrillary acidic protein (GFAP) and ionized calcium binding adaptor molecule 1 (Iba1) immunochemistry. RT-PCR and western blotting validated the significant increase in expression of glial cell-related genes GFAP and SOX10 following Al exposure compared with control rats, consistent with RNA-seq results. Collectively, these results suggest that aberrant mRNAs and lncRNAs respond to Al neurotoxicity, and that glial cell-related genes play important roles in the Al neurotoxicity mechanism. These findings provide the basis for designing targeted approaches for the treatment or prevention of Al-induced neurotoxicity.

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Acknowledgments

RNA-seq and bioinformatics analysis were performed by Novogene Company. This research was supported by the National Natural Science Foundation of China (grant no. 81430078). We are grateful to Sarah Williams, PhD, from Liwen Bianji, Edanz Group China, for editing the English text of the draft of this manuscript.

Funding

This research was supported by the National Natural Science Foundation of China (grant no. 81430078).

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Authors and Affiliations

  1. Pathology Department, Shanxi Medical University Fenyang College, Fenyang, Shanxi, 032200, China

    Yirong Xu

  2. College of Public Health, Shanxi Medical University, Taiyuan, Shanxi, 030001, China

    Yirong Xu, Huifang Zhang, Baolong Pan, Shuhui Zhang, Shan Wang & Qiao Niu

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  1. Yirong Xu
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Correspondence to Qiao Niu.

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The authors declare that they have no conflict of interest.

Ethical Approval

All the procedures involving animals were in accordance with the Guide for the Care and Use of Laboratory Animals published by the National Institutes of Health (NIH Publications No. 8023, revised 1978). This study was approved by the Animal Care and Use Committee of Shanxi Medical University. This article does not contain any studies with human participants performed by any of the authors.

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Highlights

• Sub-chronical low level Al exposure impairs rat spatial learning and memory

• Hippocampus lncRNA and mRNA profiles affected by Al were identified

• Candidate genes and signaling pathways in Al neurotoxicity were screened

• Glial cells and associated genes may be involved in Al neurotoxicity

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Xu, Y., Zhang, H., Pan, B. et al. Transcriptome-Wide Identification of Differentially Expressed Genes and Long Non-coding RNAs in Aluminum-Treated Rat Hippocampus. Neurotox Res 34, 220–232 (2018). https://doi.org/10.1007/s12640-018-9879-1

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