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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
30
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pubmed:dateCreated |
2004-7-29
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pubmed:abstractText |
Lithium is widely used to treat bipolar disorder, but its mechanism of action in this disorder is unknown. Several molecular targets of lithium have been identified, but these putative targets have not been shown to be responsible for the behavioral effects of lithium in vivo. A robust model for the effects of chronic lithium on behavior in mice would greatly facilitate the characterization of lithium action. We describe behaviors in mice that are robustly affected by chronic lithium. Remarkably, these lithium-sensitive behaviors are also observed in mice lacking one copy of the gene encoding glycogen synthase kinase-3beta (Gsk-3beta), a well established direct target of lithium. In addition, chronic lithium induces molecular changes consistent with inhibition of GSK-3 within regions of the brain that are paralleled in Gsk-3beta+/- heterozygous mice. We also show that lithium therapy activates Wnt signaling in vivo, as measured by increased Wnt-dependent gene expression in the amygdala, hippocampus, and hypothalamus. These observations support a central role for GSK-3beta in mediating behavioral responses to lithium.
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pubmed:grant |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Catnb protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Cytoskeletal Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Enzyme Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Glycogen Synthase Kinase 3,
http://linkedlifedata.com/resource/pubmed/chemical/Intercellular Signaling Peptides...,
http://linkedlifedata.com/resource/pubmed/chemical/Lithium Chloride,
http://linkedlifedata.com/resource/pubmed/chemical/Nerve Tissue Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Psychotropic Drugs,
http://linkedlifedata.com/resource/pubmed/chemical/Trans-Activators,
http://linkedlifedata.com/resource/pubmed/chemical/Wnt Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/beta Catenin,
http://linkedlifedata.com/resource/pubmed/chemical/glycogen synthase kinase 3 beta
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pubmed:status |
MEDLINE
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pubmed:month |
Jul
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pubmed:issn |
1529-2401
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pubmed:author |
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pubmed:issnType |
Electronic
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pubmed:day |
28
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pubmed:volume |
24
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
6791-8
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pubmed:dateRevised |
2011-11-2
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pubmed:meshHeading |
pubmed-meshheading:15282284-Animals,
pubmed-meshheading:15282284-Behavior, Animal,
pubmed-meshheading:15282284-Brain,
pubmed-meshheading:15282284-Brain Chemistry,
pubmed-meshheading:15282284-Cytoskeletal Proteins,
pubmed-meshheading:15282284-Dose-Response Relationship, Drug,
pubmed-meshheading:15282284-Enzyme Inhibitors,
pubmed-meshheading:15282284-Exploratory Behavior,
pubmed-meshheading:15282284-Female,
pubmed-meshheading:15282284-Glycogen Synthase Kinase 3,
pubmed-meshheading:15282284-Grooming,
pubmed-meshheading:15282284-Habituation, Psychophysiologic,
pubmed-meshheading:15282284-Heterozygote,
pubmed-meshheading:15282284-Intercellular Signaling Peptides and Proteins,
pubmed-meshheading:15282284-Lithium Chloride,
pubmed-meshheading:15282284-Male,
pubmed-meshheading:15282284-Mice,
pubmed-meshheading:15282284-Mice, Inbred C57BL,
pubmed-meshheading:15282284-Mice, Knockout,
pubmed-meshheading:15282284-Mice, Mutant Strains,
pubmed-meshheading:15282284-Motor Activity,
pubmed-meshheading:15282284-Nerve Tissue Proteins,
pubmed-meshheading:15282284-Psychotropic Drugs,
pubmed-meshheading:15282284-Random Allocation,
pubmed-meshheading:15282284-Social Behavior,
pubmed-meshheading:15282284-Startle Reaction,
pubmed-meshheading:15282284-Swimming,
pubmed-meshheading:15282284-Trans-Activators,
pubmed-meshheading:15282284-Transcription, Genetic,
pubmed-meshheading:15282284-Wnt Proteins,
pubmed-meshheading:15282284-beta Catenin
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pubmed:year |
2004
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pubmed:articleTitle |
Glycogen synthase kinase-3beta haploinsufficiency mimics the behavioral and molecular effects of lithium.
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pubmed:affiliation |
Division of Hematology-Oncology, Department of Medicine, and Howard Hughes Medical Institute, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104-6148, USA.
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pubmed:publicationType |
Journal Article,
Comparative Study,
Research Support, U.S. Gov't, P.H.S.
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