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

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Abstract
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 Alzeimer'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.