Dehydroepiandrosterone regulates astroglia reaction to denervation of olfactory glomeruli

Effects of dehydroepiandrosterone (DHEA) on glial reactions of the peripherally denervated olfactory bulb were studied in adult male rats. Denervation was achieved by destroying the olfactory mucosa with ZnSO(4) (0.17 M) irrigation of the nasal cavities. In one series of experiments, chronic DHEA treatment was applied (daily injections for 7 days, i.p., 10 mg/kg b.w. and 25 mg/kg b.w.); in the other series of experiments, animals received a single injection of DHEA (i.p., 10 mg/kg b.w., 25 mg/kg b.w. and 50 mg/kg b.w.) 2 h following ZnSO(4) treatment. To determine whether DHEA conversion to estradiol was involved in the mechanism of DHEA action on glia, a third series of experiments was carried out in which the aromatase inhibitor fadrozole (4.16 mg/ml) was administered using subcutaneously implanted osmotic minipumps. Rats were killed on day 7 after chemical denervation, and the reaction of glial cells was monitored within the olfactory bulb, using GFAP and vimentin immunohistochemistry. Qualitative changes in GFAP expression were analyzed by Western blot. Chronic DHEA treatment with both doses (10 mg/kg b.w. and 25 mg/kg b.w.) and acute DHEA treatment with the highest dose applied (50 mg/kg b.w.), inhibited the increase in GFAP expression induced by the denervation of the olfactory bulb. Furthermore, GFAP and vimentin immunostaining in the glomerular layer of the olfactory bulb were diminished in the denervated and DHEA treated groups. However, when DHEA treatment was combined with fadrozole administration, such a decrease in GFAP expression could not be detected in the chemically denervated olfactory bulb. These findings indicate that DHEA, depending on the dose applied and the mode of administration, attenuates glial reaction to denervation and may regulate glial plasticity in the olfactory glomeruli. These effects are likely to be mediated at least in part by the conversion of DHEA to estradiol.