DHEA Boosts Growth Rate of Human Neural Stem
Cells
Human neural stem cells, exposed in a lab dish
to the steroid DHEA, exhibit a remarkable uptick
in growth rates, suggesting that the hormone may
play a role in helping the brain produce new cells,
according to a new study published this week in
the online editions of the Proceedings of the
National Academy of Sciences (PNAS). The new work,
conducted by a team of scientists at the University
of Wisconsin-Madison, provides some of the first
direct evidence of the biological effects of DHEA
on the human nervous system, according to Clive
Svendsen, the study's senior author and an authority
on brain stem cells at UW-Madison's Waisman Center.
"What we saw was that DHEA significantly increased
the division of the cells," says Svendsen, a UW-Madison
professor of anatomy and neurology. "It also increased
the number of neurons produced by the stem cells,
prompting increased neurogenesis of cells in culture."
DHEA or dehydroepiandrosterone is among the most
abundant naturally occurring steroids in the blood
of young humans, but levels decline with age and
its physiological effects are poorly understood.
A synthetic form of the hormone is sold over-the-counter.
Its supposed benefits range from antiaging properties
to the prevention of cancer and heart disease,
and serving as a supplement to counter the effects
of strokes, AIDS, Alzheimer's and other diseases.
But while DHEA is readily available in health-food
stores and other venues, scientists know relatively
little about the drug and its basic biological
effects on humans. Many experts familiar with
DHEA caution against its overuse.
"We don't know much about DHEA, but this new
work adds a piece to the puzzle," says Svendsen,
who conducted the study with colleagues Masatoshi
Suzuki, Lynda S. Wright, Padma Marwah and Henry
A. Lardy, all of UW-Madison. "This is the first
real evidence of DHEA's effects on human neural
cells." Svendsen and Suzuki carried out the experiments
by growing human fetal neural stem cells in culture.
The cells form aggregates known as 'neurospheres,'
which were exposed to a cocktail of DHEA and growth
and inhibitory factors, and observed a 29 percent
increase in new brain cells compared to cells
grown in a medium with the same factors, but without
DHEA. "We saw such a pure effect of DHEA," Svendsen
says. "It's the only steroid we tested that had
such a direct effect on stem cell growth and new
neuron formation," according to Suzuki. The new
work is important because it provides a direct
window to the controversial hormone's effects
on critical human cells. Similar studies have
been conducted in mice and rats, but those models
have shortcomings that are difficult to address,
Svendsen notes.
"There are previous studies in rats that suggest
DHEA is neuroprotective, but the problem with
DHEA in rats is that it is not a major metabolite
in that animal so its effects may not be the same
as those seen in humans," he says. According to
Lardy, an eminent steroid chemist and an emeritus
UW-Madison professor of biochemistry, metabolic
products of DHEA hormone have also been shown
to aid memory retention in old mice. Despite hints
from the studies in rodents that DHEA may play
a role in enhancing the brain and memory, the
new findings reported in the PNAS article were
a surprise, says Lardy. "We assumed the compounds
we were testing would be more active than DHEA
in brain stem cells," Lardy explains. In previous
studies, Lardy, with Wisconsin biochemistry colleagues
James Ntambi and Brian Fox, showed that DHEA blocked
a step in fat synthesis. "The effects of DHEA
on brain stem cells is a completely new finding,"
says Lardy. "The problem of whether DHEA itself
is having this effect, or if there's another metabolite
of the hormone involved, still exists.
" One of the intriguing aspects of the new work,
according to Svendsen, is the possibility that
DHEA could have some positive effects on the adult
human brain. It's known that DHEA amounts fall
progressively during aging, and reduced levels
of DHEA have been reported in both adolescents
and adults with major depressive disorders. And
given the fact that adult humans have neural stem
cells that continue to make new neurons in some
parts of the brain, there is a possibility that
DHEA could play a role in moderating the genesis
of new brain cells. However, Svendsen cautions
that it is also clear that DHEA is a powerful
neurosteroid and may have other side effects.
He says it is not advisable to ingest the hormone
in the hope of increasing brainpower.
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