Antioxidant and Anti-Apoptotic Properties of Allopregnanolone in Protecting Dopaminergic Neurons from ۶-OHDA-Induced Injury

Dopaminergic neurodegeneration is associated with oxidative stress, mitochondrial dysfunction, neuroinflammation, and cell death. Allopregnanolone, a multifunctional neurosteroid, is involved in various biological processes within the body. It has been demonstrated that allopregnanolone exhibits protective effects in neurodegenerative conditions. However, its cellular mechanisms in dopaminergic neurons remain incompletely understood. Cell toxicity was induced using ۶-hydroxydopamine (۶-OHDA), and Cell survival was assessed through the MTT assay. Intracellular reactive oxygen species (ROS) and mitochondrial membrane potential were evaluated using fluorescence probes. Additionally, immunoblotting was employed to measure the levels of apoptosis biomarkers in the cells. Treatment with ۶-OHDA significantly decreased cell survival rate and exacerbated the loss of mitochondrial membrane potential. Moreover, there was a notable increase in intracellular ROS levels, the Bax/Bcl-۲ ratio, caspase-۳, and cytochrome c activity in ۶-OHDA-treated cells. Pretreatment with allopregnanolone (۲۵۰ µM) significantly mitigated these effects in cells exposed to ۶-OHDA. Furthermore, the blockade of GABAA receptors by bicuculline significantly reduced the protective effect of allopregnanolone. The data indicate that allopregnanolone's protective effects are attributed to its antioxidant and anti-apoptotic properties, suggesting its therapeutic potential for preventing dopaminergic damage.

کلیدواژه ها:

Dopaminergic neurodegeneration ، ۶-hydroxydopamine ، Allopregnanolone ، Apoptosis ، SH-SY۵Y cells