Z. Bandpey, J. Herbert

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.

Keywords (Optional):