Investigation of Autophagy-Related Gene Expressions in the Rat Model of Parkinson Disease

Objectives: Parkinson disease (PD) is characterized by protein aggregations in the cytoplasm of the dopaminergic neurons due to cellular stresses. In response to these stresses, autophagy is a conservative mechanism, and dysregulation of it results in protein aggregation. Despite the accepted prominent role of it in PD, autophagy associated-gene expression dysregulation involved in the autophagosome formation has remained largely unknown. In this study, the autophagy-related gene expressions in the rat model of PD were investigated. Materials and Methods: Male Wistar rats were divided into control, sham and PD experimental model groups. By injection of 6-hydroxydopamine (6-OHDA) into the striatum, the rat model of PD was induced. The apomorphine-induced rotation test was done 1 week before (baseline) and 4 weeks after surgery and also Nissl staining was performed for the brain sections. Then, rat substantia nigra pars compacta (SNpc) was extracted and RT-PCR was performed to detect the expression of FOXO3A gene and the autophagy-related genes (ATG). Furthermore, using Western blotting, we investigated the protein levels of ATG101. Results: Apomorphine-induced rotation test indicated significant contralateral rotations in the rat model group. Using RT-PCR, in the induction group, ATG101 was not expressed and ATG13, ATG14L, and VPS34 genes were downregulated in comparison with the control groups. Furthermore, Western blotting showed that ATG101 protein was not expressed in the model group. Conclusions: The results showed that deregulation of ATG101 expression, as a factor involved in the initial stages of the autophagy, occurs in the rat model of PD.