Palmitoylethanolamide Stimulation Induces Allopregnanolone Synthesis in C6 Cells and Primary Astrocytes: Involvement of Peroxisome-Proliferator Activated Receptor-Alpha

The study investigated the role of palmitoylethanolamide (PEA) in neurosteroidogenesis within astrocytes, focusing on its interaction with peroxisome-proliferator activated receptor (PPAR)-α. Using C6 glioma cells and primary murine astrocytes, researchers found that PEA increased the expression of steroidogenic acute regulatory protein (StAR) and cytochrome P450 enzyme (P450scc), crucial for neurosteroid formation. This effect was inhibited by GW6471, a PPAR-α antagonist, and PPAR-α silencing. PEA also elevated allopregnanolone (ALLO) levels, which was blocked by GW6471, and demonstrated antioxidative properties by reducing malondialdehyde formation, an effect partially inhibited by finasteride. The study concluded that PEA promotes ALLO synthesis through PPAR-α, contributing to its antioxidative and protective roles in the central nervous system.