Histone Deacetylase Inhibitors Promote Neurosteroid-Mediated Cell Differentiation and Enhance Serotonin-Stimulated Brain-Derived Neurotrophic Factor Gene Expression in Rat C6 Glioma Cells

The study investigated the effects of histone deacetylase (HDAC) inhibitors on glial cell differentiation using rat C6 glioma cells. It was found that HDAC inhibitors, such as trichostatin A, sodium butyrate, and valproic acid, stimulated the expression of the glial fibrillary acidic protein (GFAP) gene. This stimulation was inhibited by finasteride, which blocks the production of 5α-reduced neurosteroids. Additionally, HDAC inhibitors enhanced serotonin-stimulated brain-derived neurotrophic factor (BDNF) gene expression, an effect also negated by inhibiting 5α-reduced neurosteroid production. These findings suggested that HDAC inhibitors could promote glial cell differentiation through neurosteroid production, enhancing BDNF expression and potentially supporting neural network integrity and neuronal function.