ROTENON İLE İNDÜKLENEN İN VİTRO PARKİNSON HASTALIĞI MODELİNDE GLP-1İN NÖRON SAĞKALIMINA ETKİLERİNİN İNCELENMESİ.
Project no. 48 · Status: Kapanmış · 2016
Summary
Parkinson's disease (PD) is one the most common neurodegenerative disorder characterized by bradykinesia, tremor, rigidity and postural instability as a result of progressive degeneration of the dopaminergic neurons in substantia nigra pars compacta (SNc) and dopamine decrease in the striatum. Accumulating data recommends that combination of genetic and environmental factors including aging, exposure to pesticides, and heavy metals may have significant roles in the pathogenesis of PD. Rotenone, an organic pesticide, is commonly used for investigating the mechanism of neuronal degeneration in experimental PD models. In the present study, we aimed to investigate the effects of rotenone on SHSY5Y human neuroblastoma cells, and also the neuroprotective effects of exenatide, a GLP-1 analogue, against rotenone-induced neurotoxicity. Briefly, to induce rotenone-induced neurotoxicity, SHSY5Y cells were exposed to various doses of rotenone for 24 hours. To explore the neuroprotective effects of exenatide, different doses of exenatide were added into the medium with or without rotenone for 24 hours. Cell viability, clonegenic potential, morphological alterations, and apoptotic cell death were evaluated. Our results demonstrated a dose-dependent and significant decrease in cell viability in rotenone-exposed groups. Also, rotenone-treated group showed significant morphological alterations, decreased clonogenic potential and increased apoptosis. However, treatment of the cells with exenatide significantly improved cell viability and clonogenic activity, and reduced apoptotic cell death. In conclusion, these findings suggested that rotenone can induce neurotoxicity in neuronal cells and can be used to establish in vitro PD model. In addition, exenatide may have neuroprotective effects on neuronal cells against rotenone-induced neurotoxicity.