Dehydroepiandrosterone Stimulates Neurogenesis in Mouse Embryonic Carcinoma and Human Embryonic Stem Cell-Derived Neural Progenitors and Induces Dopaminergic Neurons (Pages: 0-0)


Azizi H *, Zare Mehrjerdy N , Shahbazy E , Baharvand H , Kiani S ,

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Objective: To evaluate the effect of Dehydroepiandrosterone (DHEA) as a neurosteroid on the rate of neurogrnesis, neural survival and proliferation of pluripotent stem cells-derived neurons, we have added DHEA on mouse P19 embryonal carcinoma cells (ECC) and human embryonic stem cells (ESCs)-neural progenitors (NPs). Materials and Methods: Flow cytometric, quantitative RT-PCR and Immunocytochemistry analysis showed the percentage of tyrosin hydroxylase (TH), Nurr1, Nestin, BrdU and Tuj1 positive cells. The expression of neuronal specific genes such as Mash1, Pax6, Tuj1,EsR, TH, was also detected by RT-PCR analysis, and also apoptosis was detect to annexinV assay. Results: In ECC-derived NPs, flow cytometric analysis of Nestin- and Tuj1-positive cells revealed that the percentages of these cells were increased significantly for the markers following DHEA treatment of the cells. Moreover, the percentages of tyrosin hydroxylase (TH)-positive cells, the marker of dopaminergic neurons significantly increased in presence of DHEA.The BrdU incorporation and Estrogen receptor (EsR) found to have increased after DHEA induction. Moreover, the apoptosis was significantly decreased after DHEA treatment. DHEA effect also confirmed on human ESCs-derived NPs by enhancement of Tuj1- and TH-immunofluorescent positive cells and TH and Nurr1 transcripts as detected by quantitative RT-PCR. Conclusion: In conclusion, these results have presented evidence DHEA is able to induce neurogenesis in mouse ECC and human ESC cells-derived NPs. This observation is related to the division of NPs and the reduction of apoptosis. Moreover, DHEA has dopaminerdic potential in the both species cells. This provides a better insight into the differentiation and maintenance of neural cells and treatment of a wide variety of neurological diseases such as Alzheimer and Parkinson by stem cells.