Linked Life Data

16943560

Source:http://linkedlifedata.com/resource/pubmed/id/16943560

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
35
pubmed:dateCreated
2006-8-31
pubmed:abstractText
Lithium is used as treatment for bipolar disorder with particular efficacy in the treatment of mania. Lithium inhibits glycogen synthase kinase 3beta (GSK-3beta) directly or indirectly via stimulation of the kinase Akt-1. We therefore investigated the possibility that transgenic mice overexpressing GSK-3beta could be of relevance to model bipolar disorder. Transgenic mice showed hypophagia, an increased general locomotor activity, and decreased habituation as assessed in an open field, an increased acoustic startle response, and again decreased habituation. The forced swim test revealed a reduced immobility in transgenic mice, but this is probably related to the hyperactivity of the animals. There were no differences in baseline and stress-induced increases of plasma adrenocorticotrophic hormone and corticosterone levels. Molecular analysis suggests compensatory mechanisms in the striatum of these transgenic mice for the overload of active GSK-3beta by dimming the endogenous GSK-3beta signaling pathway via upregulation of Akt-1 expression. Brain-derived neurotrophic factor protein levels were increased in the hippocampus of the transgenic mice. This suggests some kind of compensatory mechanism to the observed reduction in brain weight, which has been related previously to a reduced size of the somatodendritic compartment. Together, in mice overexpressing GSK-3beta, specific intracellular signaling pathways are affected, which is accompanied by altered plasticity processes and increased activity and reactivity, whereas habituation processes seem to be decreased. The behavioral observations led to the suggestion that the model at hand recapitulates hyperactivity as observed in the manic phase of bipolar disorder.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
1529-2401
pubmed:author
pubmed:issnType
Electronic
pubmed:day
30
pubmed:volume
26
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
9022-9
pubmed:dateRevised
2011-11-2
pubmed:meshHeading
pubmed-meshheading:16943560-Adrenocorticotropic Hormone, pubmed-meshheading:16943560-Animals, pubmed-meshheading:16943560-Bipolar Disorder, pubmed-meshheading:16943560-Brain-Derived Neurotrophic Factor, pubmed-meshheading:16943560-Corticosterone, pubmed-meshheading:16943560-DNA, pubmed-meshheading:16943560-Disease Models, Animal, pubmed-meshheading:16943560-Drinking, pubmed-meshheading:16943560-Eating, pubmed-meshheading:16943560-Female, pubmed-meshheading:16943560-Glycogen Synthase Kinase 3, pubmed-meshheading:16943560-Hippocampus, pubmed-meshheading:16943560-Hyperkinesis, pubmed-meshheading:16943560-Male, pubmed-meshheading:16943560-Mice, pubmed-meshheading:16943560-Mice, Transgenic, pubmed-meshheading:16943560-Motor Activity, pubmed-meshheading:16943560-Photoperiod, pubmed-meshheading:16943560-Signal Transduction, pubmed-meshheading:16943560-Startle Reaction, pubmed-meshheading:16943560-Swimming
pubmed:year
2006
pubmed:articleTitle
Transgenic mice overexpressing glycogen synthase kinase 3beta: a putative model of hyperactivity and mania.
pubmed:affiliation
Division of Psychiatry, Johnson & Johnson Pharmaceutical Research and Development, B-2340 Beerse, Belgium.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't