Neurosteroid dehydroepiandrosterone attenuates 6-hydroxydopamine-induced apoptosis in a cell model of Parkinson's disease

Parkinson’s disease is a progressive neurodegenerative disorder characterized by progressive death of midbrain dopaminergic neurons. Neurosteroid dehydroepiandrosteone (DHEA) is synthesized de novo in brain glial cells and its concentration is particularly high in the brain, which dramatically decreases by aging. DHEA has neuroprotective activity against different types of neural injuries. In this study, we investigated the effects of DHEA on 6-hydroxydopamine (6-OHDA)-induced toxicity in rat pheochromocytoma (PC12) cells as an in vitro model of Parkinson’s disease.

Cell damage was induced by 150μM 6-OHDA and the cell survival rate was examined by MTT assay. The level of intracellular reactive oxygen species (ROS) was determined with a 2,7-dichlorofluorescein diacetate probe. Immunoblotting was also employed to determine the level of biochemical markers of neural apoptosis in PC12 cells.

The data demonstrated toxic effect of 6-OHDA by reducing cell viability in a dose-dependent manner. Furthermore, activated caspase-3 and Bax/Bcl2 ratio were significantly increased in 6-OHDA-treated cells. Incubation of cells with DHEA (400 and 600μg/ml) decreased cell damage.

Our results suggest that DHEA has protective effects against 6-OHDA-induced neural damage. The mechanisms of these effects may be due to the attenuation of neural apoptosis and suggest therapeutic potential of this neurosteroid in the treatment of Parkinson’s disease.</div>