Effect of Dehydroepiandrosterone and Related Steroids on Neurogenesis in Adult Rat Brain
Z. Bandpey and J. Herbert
Department of Anatomy, University of Cambridge, Cambridge CB2 3DY, UK
Most neurons in adult central nervous system (CNS) are terminally
differentiated and are not replaced when they die. Evidence now exist
that small populations of neurons are formed in the adult olfactory
bulb and hippocampus. In adult hippocampus, newly born neurons
originate from putative stem cells that exist in the subgranular zone
of the dentate gyrus. Progeny of these putative stem cells
differentiate into neurons in the granular layer within a month of the
cells birth, and this late neurogenesis continues throughout the adult
life of all mammals. The rate of neurogenesis is not only dependent of
the potentials of these cells but also environmental factors, one of
which being hormonal environment. Neurogenesis in dentate gyrus is
decreased by glucocorticoids, a steroid produced by the adrenal glands
in response to stress. Dehydroepiandrosterone (DHEA) is another steroid
which is not only produced by adrenal glands but also by the brain and
is the most abundant steroid in human blood. DHEA is an intermediate in
biosynthesis of testosterone and estrogens but also exert several
physiological effects independent of the sex hormones. It has recently
been reported that DHEA stimulates the generation of new cells in the
dentate gyrus of the hippocampus and it counteracts the suppressive
effect of glucocorticoids. In this study we have confirmed that chronic
treatment with DHEA increases cell proliferation in dentate gyrus of
adult rats. We tested whether derivatives of DHEA are more active than
the parent steroid. Fluasterone (16α-fluoro-5-androsten-17-one)
dose dependently reduced the number of new cells in dentate gyrus.
Furthermore, fluasterone counteracts the DHEA induced increase in
neurogenesis. The 7-oxo derivative of DHEA induced a significant
increased cell proliferation in dentate gyrus in adult rat brain. Our
results indicate that effect of DHEA on neurogenesis is partly through
its further conversion to more polar compounds, such as 7-oxo
metabolites.
Key words:
Neurogenesis, hippocampus, DHEA, 7-OXO-DHEA
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