Evaluation of the role of endoplasmic reticulum stress in the progress of 6-hydroxydopamine-induced Parkinsonism in rat

In this study, using evaluation of the expression of two specific proteins of endoplasmic reticulum (ER) stress, GRP78 and CHOP in the striatum and substantia nigra (SN) in the 6-hydroxydopamine (6-OHDA) animal model of Parkinson’s disease (PD), the role of this stress was evaluated in the progress of Parkinson's disease (PD). 

6-OHDA was injected into medial forebrain bundle. Behavioral tests were carried out in the second, forth, sixth and eighth weeks after the toxin. In the eighth week, the brain of some rats was perfused and immunohistochemical (IHC) assessments were performed to evaluate the survival of dopaminergic neurons in SN and also the expression of GRP78 and CHOP in striatum. The brain of other rats was freshly removed and the expression of GRP78 and CHOP in SN was evaluated using western blotting.

The severity of behavioral symptoms increased progressively in 6-OHDA- treated rats and reached to maximum in the eighth week. IHC assessments revealed that more than 80% of dopaminergic neurons in SN were lost in these rats. These assessments also showed that only 5% of the cells in striatum of control rats expressed GRP78 and CHOP. On the other hand, about 42% of these cells in 6-OHDA- treated rats expressed these proteins. Furthermore, expression of GRP78 and CHOP in SN of 6-OHDA- treated rats increased 400% as compared to control rats.

ER stress involves in progress of 6-OHDA-induced parkinsonism in rat indicating this stress may have a role in progress of PD in human beings.