Chronic lithium treatment affects rat brain and serum dehydroepiandrosterone (DHEA) and DHEA-sulphate (DHEA-S) levels
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 sug...
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| Veröffentlicht in: | The international journal of neuropsychopharmacology 2004-03, Vol.7 (1), p.71-75 |
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| container_title | The international journal of neuropsychopharmacology |
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| creator | Maayan, Rachel Shaltiel, Galit Poyurovsky, Michael Ramadan, Edward Morad, Oren Nechmad, Allon Weizman, Abraham Agam, Galila |
| description | 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 Li's 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 Li's mood stabilization. |
| doi_str_mv | 10.1017/S1461145703003821 |
| format | Article |
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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 Li's 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 Li's mood stabilization.</description><identifier>ISSN: 1461-1457</identifier><identifier>EISSN: 1469-5111</identifier><identifier>DOI: 10.1017/S1461145703003821</identifier><identifier>PMID: 14725722</identifier><language>eng</language><publisher>Cambridge, UK: Cambridge University Press</publisher><subject>Animals ; Brain Chemistry - drug effects ; Brief Reports ; Cerebral Cortex - drug effects ; Cerebral Cortex - metabolism ; Dehydroepiandrosterone - blood ; Dehydroepiandrosterone - metabolism ; Dehydroepiandrosterone Sulfate - blood ; Dehydroepiandrosterone Sulfate - metabolism ; Hippocampus - drug effects ; Hippocampus - metabolism ; Lithium - pharmacology ; Male ; Radioimmunoassay ; Rats ; Rats, Sprague-Dawley</subject><ispartof>The international journal of neuropsychopharmacology, 2004-03, Vol.7 (1), p.71-75</ispartof><rights>2004 Collegium Internationale Neuropsychopharmacologicum</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c411t-6f55260bbc1846a5b0a0e777046c414d6d28894afb583626cff09f615ef957d3</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/14725722$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Maayan, Rachel</creatorcontrib><creatorcontrib>Shaltiel, Galit</creatorcontrib><creatorcontrib>Poyurovsky, Michael</creatorcontrib><creatorcontrib>Ramadan, Edward</creatorcontrib><creatorcontrib>Morad, Oren</creatorcontrib><creatorcontrib>Nechmad, Allon</creatorcontrib><creatorcontrib>Weizman, Abraham</creatorcontrib><creatorcontrib>Agam, Galila</creatorcontrib><title>Chronic lithium treatment affects rat brain and serum dehydroepiandrosterone (DHEA) and DHEA-sulphate (DHEA-S) levels</title><title>The international journal of neuropsychopharmacology</title><addtitle>Int. J. Neuropsychopharm</addtitle><description>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 Li's inhibition of PAP phosphatase leads to elevated PAP levels resulting in inhibition of sulphation and reduction in brain DHEA-S levels. 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Our results show that Li administration lowered frontal cortex and hippocampus DHEA and DHEA-S levels, in line with our hypothesis assuming that Li's 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 Li's mood stabilization.</abstract><cop>Cambridge, UK</cop><pub>Cambridge University Press</pub><pmid>14725722</pmid><doi>10.1017/S1461145703003821</doi><tpages>5</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | The international journal of neuropsychopharmacology, 2004-03, Vol.7 (1), p.71-75 |
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| language | eng |
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| source | MEDLINE; Oxford Journals Open Access Collection; EZB-FREE-00999 freely available EZB journals |
| subjects | Animals Brain Chemistry - drug effects Brief Reports Cerebral Cortex - drug effects Cerebral Cortex - metabolism Dehydroepiandrosterone - blood Dehydroepiandrosterone - metabolism Dehydroepiandrosterone Sulfate - blood Dehydroepiandrosterone Sulfate - metabolism Hippocampus - drug effects Hippocampus - metabolism Lithium - pharmacology Male Radioimmunoassay Rats Rats, Sprague-Dawley |
| title | Chronic lithium treatment affects rat brain and serum dehydroepiandrosterone (DHEA) and DHEA-sulphate (DHEA-S) levels |
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