| Overview of the mechanism of action of lithium in the brain: fifty-year update. | |
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MedLine Citation:
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PMID: 10826655 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Since its discovery, lithium has been shown to act upon various neurotransmitter systems at multiple levels of signaling in the brain. Lithium, affecting each neurotransmitter system within complex interactive neuronal networks, is suggested to restore the balance among aberrant signaling pathways in critical regions of the brain. Recent molecular studies have revealed the action of lithium on signal transduction mechanisms, such as phosphoinositide hydrolysis, adenylyl cyclase, G protein, glycogen synthase kinase-3beta, protein kinase C, and its substrate myristoylated alanine-rich C kinase substrate. Such effects are thought to trigger long-term changes in neuronal signaling patterns that account for the prophylactic properties of lithium in the treatment of bipolar disorder. Through its effects on glycogen synthase kinase-3beta and protein kinase C, lithium may alter the level of phosphorylation of cytoskeletal proteins, which leads to neuroplastic changes associated with mood stabilization. Chronic lithium regulates transcriptional factors, which in turn may modulate the expression of a variety of genes that compensate for aberrant signaling associated with the pathophysiology of bipolar disorder. Future studies on long-term neuroplastic changes caused by lithium in the brain will set the stage for new drug-discovery opportunities. |
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Authors:
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R H Lenox; C G Hahn |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.; Review |
Journal Detail:
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Title: The Journal of clinical psychiatry Volume: 61 Suppl 9 ISSN: 0160-6689 ISO Abbreviation: J Clin Psychiatry Publication Date: 2000 |
Date Detail:
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Created Date: 2000-05-31 Completed Date: 2000-05-31 Revised Date: 2009-11-19 |
Medline Journal Info:
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Nlm Unique ID: 7801243 Medline TA: J Clin Psychiatry Country: UNITED STATES |
Other Details:
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Languages: eng Pagination: 5-15 Citation Subset: IM |
Affiliation:
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Department of Psychiatry, University of Pennsylvania, Philadelphia 19104-6140, USA. rlenox@mail.med.upenn.edu |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Bipolar Disorder
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drug therapy,
metabolism,
physiopathology Brain / drug effects* Brain Chemistry / drug effects Cytoskeletal Proteins / drug effects, metabolism GTP-Binding Proteins / drug effects, metabolism Gene Expression / drug effects Humans Ion Transport / drug effects Lithium / pharmacokinetics, pharmacology*, therapeutic use Neuronal Plasticity / drug effects Neuropeptides / drug effects, physiology Neurotransmitter Agents / physiology Phosphorylation / drug effects Protein Kinase C / drug effects, metabolism Protein Kinases / drug effects, metabolism Signal Transduction / drug effects Synaptic Transmission / drug effects |
| Grant Support | |
ID/Acronym/Agency:
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R01 MH56247-01/MH/NIMH NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Cytoskeletal Proteins; 0/Neuropeptides; 0/Neurotransmitter Agents; 7439-93-2/Lithium; EC 2.7.-/Protein Kinases; EC 2.7.11.13/Protein Kinase C; EC 3.6.1.-/GTP-Binding Proteins |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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