Is brain dehydroepiandrosterone synthesis modulated by free radicals in mice?
Maayan R; Touati-Werner D; Ram E; Galdor M; Weizman A Laboratory of Biological Psychiatry, Felsenstein Medical Research Center, Petah Tikva 49100, Israel. rmayan@post.tau.ac.il Dehydroepiandrosterone (DHEA) is a neurosteroid synthesized de novo in the brain, in addition to the periphery, modulating some membrane, ion-gated channel neurotransmitter receptors. P450-17alpha-hydroxylase activity converting pregnenolone to DHEA, has not yet been identified in the brain of rodents. Studies in brain-derived primary cultures and cell lines, suggest a possible alternative pathway for DHEA synthesis involving oxygenated hydroxyperoxides. We investigated DHEA synthesis in the brains of castrated male mice before and after treatment with N-acetylcysteine amide (AD4) (a newly developed brain penetrating antioxidant). We found a significant increase in brain DHEA level 24 h after castration, which was totally blocked by AD4. This blockade of castration-induced increased brain DHEA synthesis, support
