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

Transcriptome-Wide Identification of Differentially Expressed Genes and Long Non-coding RNAs in Aluminum-Treated Rat Hippocampus
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铝处理大鼠海马差异表达基因和长非编码 RNA 的全转录组鉴定

DOI:
10.1007/s12640-018-9879-1
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发表时间:
2018-02
影响因子:
3.7
通讯作者:
Qiao Niu
Qiao Niu
中科院分区:
医学3区
文献类型:
--
作者:
Yirong Xu;Huifang Zhang;Baolong Pan;Shuhui Zhang;Shan Wang;Qiao Niu

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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 genesGFAPandSOX10following 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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