Dehydroepiandrosterone and its sulfated derivative reduce neuronal death and enhance astrocytic differentiation in brain cell cultures.

Human studies of dehydroepiandrosterone (DHEA) and dehydroepiandrosterone sulfate (DHEA-S) have shown age-related changes in serum levels of these two sex hormone precursors. The levels of both DHEA and DHEA-S are characterized by monotonic decreases after puberty in females and after 20-24 yr of age in males. Further studies have shown that DHEA and DHEA-S levels are significantly low or close to minimal at ages when the incidence of senile dementia of Alzheimer's type (SDAT) begins to increase. We propose that DHEA and DHEA-S play a significant role in normal function of neuronal cells and that supplementation with them may prevent neuronal loss and/or damage. In the present study, using methods of immunocytochemistry, autoradiography, and scanning electron microscopy, we show that a supplement of as little as 10(-8) M DHEA or DHEA-S greatly increases neuronal survival and differentiation and reduces astroglial proliferation rates in mouse brain cells in cultures. These results suggest that correcting the DHEA and the DHEA-S deficit may prevent and/or improve the SDAT condition in humans.