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 like trichostatin A, sodium butyrate, and valproic acid stimulated the expression of glial fibrillary acidic protein (GFAP) and enhanced serotonin-stimulated brain-derived neurotrophic factor (BDNF) gene expression. These effects were mediated through the production of 5α-reduced neurosteroids, as their inhibition by finasteride reduced the stimulatory effects. The findings suggested that HDAC inhibitors could promote glial cell differentiation and enhance BDNF expression, potentially preserving neural network integrity and improving neuronal function.