PT  - JOURNAL ARTICLE
AU  - Jos Prickaerts
AU  - Dieder Moechars
AU  - Kim Cryns
AU  - Ilse Lenaerts
AU  - Hansfried van Craenendonck
AU  - Ilse Goris
AU  - Guy Daneels
AU  - J. Adriaan Bouwknecht
AU  - Thomas Steckler
TI  - Transgenic Mice Overexpressing Glycogen Synthase Kinase 3β: A Putative Model of Hyperactivity and Mania
AID  - 10.1523/JNEUROSCI.5216-05.2006
DP  - 2006 Aug 30
TA  - The Journal of Neuroscience
PG  - 9022--9029
VI  - 26
IP  - 35
4099  - http://www.jneurosci.org/content/26/35/9022.short
4100  - http://www.jneurosci.org/content/26/35/9022.full
SO  - J. Neurosci.2006 Aug 30; 26
AB  - Lithium is used as treatment for bipolar disorder with particular efficacy in the treatment of mania. Lithium inhibits glycogen synthase kinase 3β (GSK-3β) directly or indirectly via stimulation of the kinase Akt-1. We therefore investigated the possibility that transgenic mice overexpressing GSK-3β 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-3β by dimming the endogenous GSK-3β 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-3β, 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.