Transcriptome profiling of five brain regions in a 6-hydroxydopamine rat model of Parkinson's disease

Background Parkinson's disease (PD) is a neurodegenerative disease, and its pathogenesis is unclear. Previous studies mainly focus on the lesions of substantia nigra (SN) and striatum (Str) in PD. However, lesions are not limited. The olfactory bulb (OB), subventricular zone (SVZ), and hippocampus (Hippo) are also affected in PD. Aim To reveal gene expression changes in the five brain regions (OB, SVZ, Str, SN, and Hippo), and to look for potential candidate genes and pathways that may be correlated with the pathogenesis of PD. Materials and methods We established control group and 6-hydroxydopamine (6-OHDA) PD model group, and detected gene expressions in the five brain regions using RNA-seq and real-time quantitative polymerase chain reaction (RT-qPCR). We further analyzed the RNA-seq data by bioinformatics. Results We identified differentially expressed genes (DEGs) in all five brain regions. The DEGs were significantly enriched in the dopaminergic synapse and retrograde endocannabinoid signaling, and Gi/o-GIRK is the shared cascade in the two pathways. We further identified Ephx2, Fam111a, and Gng2 as the potential candidate genes in the pathogenesis of PD for further studies. Conclusion Our study suggested that gene expressions change in the five brain regions following exposure to 6-OHDA. The dopaminergic synapse, retrograde endocannabinoid signaling, and Gi/o-GIRK may be the key pathways and cascade of the synaptic damage in 6-OHDA PD rats. Ephx2, Fam111a, and Gng2 may play critical roles in the pathogenesis of PD.

Automated summary

This study revealed gene expression changes in the five brain regions following exposure to 6-hydroxydopamine in PD rats, identifying key pathways and cascade involved in synaptic damage. The dopaminergic synapse, retrograde endocannabinoid signaling, and Gi/o-GIRK were highlighted as potential key pathways. Potential candidate genes such as Ephx2, Fam111a, and Gng2 were identified for further studies on the pathogenesis of PD.