Neurogenic and mitotic effects of dehydroepiandrosterone on neuronal-competent marrow mesenchymal stem cells.

To establish whether dehydroepiandrosterone (DHEA) as a neurosteroid could enhance the rate of neuronal differentiation in neuronal-competent bone marrow mesenchymal stem cells (BM-MSCs), we added DHEA before and after plating the neurosphere-like aggregates. Flow cytometric analysis of Tubulin-III and Tau positive cells revealed that the percentages of these cells were increased significantly for the two markers following DHEA treatment at both stages. Moreover, Western blot analysis revealed that Tubulin-III protein was strongly induced by DHEA. The expression of neuronal specific genes such as Isl-1, Tubulin III, Pax6 and Nestin was also detected by RT-PCR analysis as well as BrdU incorporation and found to have increased significantly after DHEA induction. In conclusion, these results provide evidence that DHEA can affect neuronal-competent MSCs in inducing the expression of a comprehensive set of genes and proteins that define neuronal cells. DHEA was also able to induce the division of neuronal-competent MSCs, thereby increasing the number of cells with major neuronal characteristics. To our knowledge, this is the first report which shows that DHEA can induce the division and differentiation of MSCs into neurons in vitro and should provide an improved basis for new treatments using MSCs of a wide variety of neurological diseases.