مرکز منطقه ای اطلاع رساني علوم و فناوري - The Relationship Between Mitochondrial, Oxidative, Apoptotic Parameters and PI3K/Akt Pathway in Animal Model of Parkinson’s Disease

Abstract :

Parkinson s disease (PD) is a neurodegenerative disorder, characterized with progressive loss of dopamine-generating neurons. Neurotoxin-induced animal models of PD mimic clinical and pathological findings of PD. Lately researchers have started focusing on the novel therapeutical strategies that have neuroprotective effects and prognostic biomarkers. Thus, the PI3K/Akt signaling pathway, which regulates cell survival, is attracting increasing amounts of attention. Investigation of molecular alterations related with this pathway might aid in improvisation of novel treatment methods and biomarkers for PD. However, it is not possible to determine molecular changes in brain tissues of PD cases in different stages of the disease. In this study, we aimed to examine the changes in the expression of PI3K/Akt factors during the course of PD and their association with clinical features. Thus, we established a C57BL/6 mouse model of PD by administrating rotenone, which has been shown to increase oxidative stress. Gene expression levels of mTOR, DJ-1 and PTEN that regulate Akt-1, and caspase-3, caspase-9 and Bcl-2 that are regulated by Akt- 1 were examined in brain tissues obtained in consecutive weeks. Rigidity, bradikinesia and postural changes were observed in rotenone-treated mice. Moreover tyrosine hydroxylase positive neurons were decreased in substantia nigra, whereas cerebral apoptotic neurons were increased. Levels of Bcl-2 significantly decreased in rotenone-treated mice as compared to the control group (p 0,05). On the other hand Akt-1 was found to decrease slightly and mTOR was found to increase slightly, whereas there were no changes in caspase-3, caspase-9, DJ-1 and PTEN expression levels. There was a weak correlation between caspase-3, mTOR, Bcl-2 levels and clinical parameters. The sole occurrence of significant expression change in Bcl-2 suggests that rotenone induces PH through non-PI3K/Akt mechanisms. The absence of alteration in caspase-3 and caspase-9 expression levels implies that caspase-independent apoptosis is involved in PD pathogenesis. Mice with severe clinical symptoms showed down-regulated Bcl-2 expression suggesting that Bcl-2 might be used as a prognostic biomarker in PD cases.