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Overview of the mechanism of action of lithium in the brain: fifty-year update.
J Clin Psychiatry. 2000; 61 Suppl 9:5-15.JC

Abstract

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+Show Affiliations

Lenox RH
Department of Psychiatry, University of Pennsylvania, Philadelphia 19104-6140, USA. rlenox@mail.med.upenn.edu
Hahn CG
No affiliation info available

MeSH

Bipolar DisorderBrainBrain ChemistryCytoskeletal ProteinsGTP-Binding ProteinsGene ExpressionHumansIon TransportLithiumNeuronal PlasticityNeuropeptidesNeurotransmitter AgentsPhosphorylationProtein Kinase CProtein KinasesSignal TransductionSynaptic Transmission

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.
Review

Language

eng

PubMed ID

10826655

Citation

Lenox, R H., and C G. Hahn. "Overview of the Mechanism of Action of Lithium in the Brain: Fifty-year Update." The Journal of Clinical Psychiatry, vol. 61 Suppl 9, 2000, pp. 5-15.
Lenox RH, Hahn CG. Overview of the mechanism of action of lithium in the brain: fifty-year update. J Clin Psychiatry. 2000;61 Suppl 9:5-15.
Lenox, R. H., & Hahn, C. G. (2000). Overview of the mechanism of action of lithium in the brain: fifty-year update. The Journal of Clinical Psychiatry, 61 Suppl 9, 5-15.
Lenox RH, Hahn CG. Overview of the Mechanism of Action of Lithium in the Brain: Fifty-year Update. J Clin Psychiatry. 2000;61 Suppl 9:5-15. PubMed PMID: 10826655.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Overview of the mechanism of action of lithium in the brain: fifty-year update. AU - Lenox,R H, AU - Hahn,C G, PY - 2000/5/29/pubmed PY - 2000/6/3/medline PY - 2000/5/29/entrez SP - 5 EP - 15 JF - The Journal of clinical psychiatry JO - J Clin Psychiatry VL - 61 Suppl 9 N2 - 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. SN - 0160-6689 UR - https://www.unboundmedicine.com/medline/citation/10826655/Overview_of_the_mechanism_of_action_of_lithium_in_the_brain:_fifty_year_update_ L2 - http://www.psychiatrist.com/jcp/article/pages/2000/v61s09/v61s0902.aspx DB - PRIME DP - Unbound Medicine ER -