Transcriptome sequencing in a 6-hydroxydopamine rat model of Parkinson's disease.

Abstract

The neurotoxin 6-hydroxydopamine (6-OHDA) has been widely exploited as a tool for modeling Parkinson's disease (PD) in the rat. This study aimed to provide a comprehensive profile of the mRNAs and long noncoding RNAs (lncRNAs) in rats treated with 6-OHDA as a model of PD. Female SPF Wistar rats were randomly divided into two groups: a PD model group and a control group. The PD model was induced by 6-OHDA injection. RNA-seq analysis was performed on 6-OHDA-treated rats and corresponding controls. Novel lncRNAs were identified. Differentially expressed genes (DEGs) and differentially expressed lncRNAs were identified in the PD group compared with controls. Gene Ontology function and pathway enrichment analyses were conducted on the DEGs, followed by construction of a protein-protein interaction (PPI) network. In addition, prediction of lncRNA target genes and function prediction of lncRNAs were performed. Moreover, microRNAs (miRNAs) that interacted with the DEGs and differentially expressed lncRNAs were predicted to construct a miRNA-lncRNA-mRNA regulatory network. A total of 536 DEGs and 512 differentially expressed lncRNAs (44 up-regulated and 10 down-regulated known lncRNAs; 407 up-regulated and 51 down-regulated novel lncRNAs) were identified in the PD rat model compared with controls. The DEGs and target genes of lncRNAs were mainly associated with the innate immune response, 2'-5'-oligoadenylate synthetase activity, GTPase activity, GTP binding and the RIG-I-like receptor signaling pathway. IRF7 and ISG15 were hub proteins in the PPI network. Many mRNAs and lncRNAs interacted with other molecules in a competing endogenous RNA network, such as MAS1, TMPRSS2, NPTX1, XLOC_016191, XLOC_026924 and XLOC_005439. We conclude that IRF7, ISG15, MAS1, TMPRSS2, NPTX1, XLOC_016191, XLOC_026924 and XLOC_005439 may contribute critical roles in the pathogenesis of PD.