title: Chronic lithium treatment affects rat brain and serum dehydroepiandrosterone (DHEA) and DHEA-sulphate (DHEA-S) levels.
abstract: 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.
authors.affiliation: Laboratory of Biological Psychiatry, Felsentein Medical Research Center, Beilinson Campus, Petah Tikva and Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
authors.forename: Rachel
authors.initials: R
authors.lastname: Maayan
authors.forename: Galit
authors.initials: G
authors.lastname: Shaltiel
authors.forename: Michael
authors.initials: M
authors.lastname: Poyurovsky
authors.forename: Edward
authors.initials: E
authors.lastname: Ramadan
authors.forename: Oren
authors.initials: O
authors.lastname: Morad
authors.forename: Allon
authors.initials: A
authors.lastname: Nechmad
authors.forename: Abraham
authors.initials: A
authors.lastname: Weizman
authors.forename: Galila
authors.initials: G
authors.lastname: Agam
mesh_terms: D000818:Animals; D001923:Brain Chemistry / Q000187:drug effects*; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D003687:Dehydroepiandrosterone / Q000097:blood / Q000378:metabolism*; D019314:Dehydroepiandrosterone Sulfate / Q000097:blood / Q000378:metabolism*; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D008094:Lithium / Q000494:pharmacology*; D008297:Male; D011863:Radioimmunoassay; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D003687:Dehydroepiandrosterone; D019314:Dehydroepiandrosterone Sulfate; D008094:Lithium