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.