Mitotic and neurogenic effects of DHEA on human neural stem cell cultures

James Michael Howard jmhoward at arkansas.net
Fri Feb 20 13:53:24 EST 2004


Proc Natl Acad Sci U S A. 2004 Feb 18 [Epub ahead of print]	Links
Mitotic and neurogenic effects of dehydroepiandrosterone (DHEA) on human neural
stem cell cultures derived from the fetal cortex.

Suzuki M, Wright LS, Marwah P, Lardy HA, Svendsen CN.

Dehydroepiandrosterone (DHEA) is a neurosteroid with potential effects on
neurogenesis and neuronal survival in humans. However, most studies on DHEA have
been performed in rodents, and there is little direct evidence for biological
effects on the human nervous system. Furthermore, the mechanism of its action is
unknown. Here, we show that DHEA significantly increased the growth rates of
human neural stem cells derived from the fetal cortex and grown with both
epidermal growth factor (EGF) and leukemia inhibitory factor (LIF). However, it
had no effect on cultures grown in either factor alone, suggesting a specific
action on the EGF/LIF-responsive cell. Precursors of DHEA such as pregnenolone
or six of its major metabolites, had no significant effect on proliferation
rates. DHEA did not alter the small number (<3%) of newly formed neuroblasts or
the large number (>95%) of nestin-positive precursors. However, the number of
glial fibrillary acidic protein-positive cells, its mRNA, and protein were
significantly increased by DHEA. We found both N-methyl-D-aspartate and sigma 1
antagonists, but not GABA antagonists, could completely eliminate the effects of
DHEA on stem cell proliferation. Finally we asked whether the
EGF/LIF/DHEA-responsive stem cells had an increased potential for neurogenesis
and found a 29% increase in neuronal production when compared to cultures grown
in EGF/LIF alone. Together these data suggest that DHEA is involved in the
maintenance and division of human neural stem cells. Given the wide availability
of this neurosteroid, this finding has important implications for future use.





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