Maayan Rachel, Shaltiel Galit, Poyurovsky Michael, Ramadan Edward, Morad Oren, Nechmad Allon, Weizman Abraham, Agam Galila
Laboratory of Biological Psychiatry, Felsentein Medical Research Center, Beilinson Campus, Petah Tikva and Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
Int J Neuropsychopharmacol. 2004 Mar;7(1):71-5. doi: 10.1017/S1461145703003821. Epub 2004 Jan 16.
Lithium (Li) is an established effective treatment for bipolar disorder. However, the molecular mechanism of its action is still unknown. Dehydroepiandrosterone (DHEA) and its sulphate ester (DHEA-S) are adrenal hormones also synthesized de novo in the brain as neurosteroids. Recent studies have suggested that DHEA has mood-elevating properties and may demonstrate antidepressant effects. 3(2)-Phosphoadenosine 5-phosphate (PAP) phosphatase is a novel Li-inhibitable enzyme involved in sulphation processes. In the present study we examined the impact of 10 d Li treatment on serum and brain DHEA and DHEA-S levels in rats. Our results show that Li administration lowered frontal cortex and hippocampus DHEA and DHEA-S levels, in line with our hypothesis assuming that Lis inhibition of PAP phosphatase leads to elevated PAP levels resulting in inhibition of sulphation and reduction in brain DHEA-S levels. Future studies should address the involvement of neurosteroids in the mechanism of Lis mood stabilization.
