{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,9]],"date-time":"2026-01-09T17:17:23Z","timestamp":1767979043937,"version":"3.49.0"},"reference-count":54,"publisher":"The Company of Biologists","issue":"5-6","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2009,4,30]]},"abstract":"<jats:title>SUMMARY<\/jats:title>\n               <jats:p>Bipolar mood disorder (manic depression) is a major psychiatric disorder whose molecular origins are unknown. Mood stabilisers offer patients both acute and prophylactic treatment, and experimentally, they provide a means to probe the underlying biology of the disorder. Lithium and other mood stabilisers deplete intracellular inositol and it has been proposed that bipolar mood disorder arises from aberrant inositol (1,4,5)-trisphosphate [IP3, also known as Ins(1,4,5)P3] signalling. However, there is no definitive evidence to support this or any other proposed target; a problem exacerbated by a lack of good cellular models. Phosphatidylinositol (3,4,5)-trisphosphate [PIP3, also known as PtdIns(3,4,5)P3] is a prominent intracellular signal molecule within the central nervous system (CNS) that regulates neuronal survival, connectivity and synaptic function. By using the genetically tractable organism Dictyostelium, we show that lithium suppresses PIP3-mediated signalling. These effects extend to the human neutrophil cell line HL60. Mechanistically, we show that lithium attenuates phosphoinositide synthesis and that its effects can be reversed by overexpression of inositol monophosphatase (IMPase), consistent with the inositol-depletion hypothesis. These results demonstrate a lithium target that is compatible with our current knowledge of the genetic predisposition for bipolar disorder. They also suggest that lithium therapy might be beneficial for other diseases caused by elevated PIP3 signalling.<\/jats:p>","DOI":"10.1242\/dmm.001271","type":"journal-article","created":{"date-parts":[[2009,4,22]],"date-time":"2009-04-22T03:13:48Z","timestamp":1240370028000},"page":"306-312","source":"Crossref","is-referenced-by-count":43,"title":["The mood stabiliser lithium suppresses PIP3 signalling in Dictyostelium and human cells"],"prefix":"10.1242","volume":"2","author":[{"given":"Jason S.","family":"King","sequence":"first","affiliation":[{"name":"Cardiff School of Biosciences, Cardiff University, Museum Avenue, Cardiff CF10 3AX, UK"},{"name":"Present address: CRUK-Beatson Institute for Cancer research, Garscube Estate, Switchback Road, Glasgow G61 1BD, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Regina","family":"Teo","sequence":"additional","affiliation":[{"name":"Cardiff School of Biosciences, Cardiff University, Museum Avenue, Cardiff CF10 3AX, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jonathan","family":"Ryves","sequence":"additional","affiliation":[{"name":"Cardiff School of Biosciences, Cardiff University, Museum Avenue, Cardiff CF10 3AX, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jonathan V.","family":"Reddy","sequence":"additional","affiliation":[{"name":"Cardiff School of Biosciences, Cardiff University, Museum Avenue, Cardiff CF10 3AX, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Owen","family":"Peters","sequence":"additional","affiliation":[{"name":"Cardiff School of Biosciences, Cardiff University, Museum Avenue, Cardiff CF10 3AX, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ben","family":"Orabi","sequence":"additional","affiliation":[{"name":"School of Biological Sciences, Royal Holloway, University of London, Egham, Surrey TW20 0EX, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Oliver","family":"Hoeller","sequence":"additional","affiliation":[{"name":"MRC Laboratory of Molecular Biology, Hills Road, Cambridge CB2 2QH, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robin S. 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