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Transgenic Mice Overexpressing Glycogen Synthase Kinase 3β: A Putative Model of Hyperactivity and Mania
Open accessAbstract
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.
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“transgenic mice overexpressing the circadian modulator, GSK3β, are hyperactive, have reduced immobility in the forced swim test (indicative of lower depression-like behavior), and an increased startle response (Prickaerts et al., 2006).”
From Circadian genes, rhythms and the biology of mood disorders (2007) · cites this paper as Prickaerts et al., 2006
In the citing paper
“transgenic mice overexpressing the circadian modulator, GSK3β, are hyperactive, have reduced immobility in the forced swim test (indicative of lower depression-like behavior), and an increased startle response (Prickaerts et al., 2006).”
From Circadian genes, rhythms and the biology of mood disorders (2007) · cites this paper as Prickaerts et al., 2006
In the citing paper
“transgenic mice overexpressing the circadian modulator, GSK3β, are hyperactive, have reduced immobility in the forced swim test (indicative of lower depression-like behavior), and an increased startle response (Prickaerts et al., 2006).”
From Circadian genes, rhythms and the biology of mood disorders (2007) · cites this paper as Prickaerts et al., 2006
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Metadata
- Authors
- Prickaerts, J., Moechars, D., Cryns, K., Lenaerts, I., van Craenendonck, H., Goris, I., Daneels, G., Bouwknecht, J. A., & Steckler, T.
- Affiliations
- Janssen Research & Development (United States) (US)
- Corresponding author
- Steckler, Thomas
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2006-08-30
- Volume
- 26
- Issue
- 35
- Pages
- 9022-9029
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC6675350
- OpenAlex
- W1963600261
- Cited by
- 341
- References
- 59
- Citations by year
- 2026: 5 · 2025: 5 · 2024: 7 · 2023: 7 · 2022: 13 · 2021: 14 · 2020: 17 · 2019: 7 · 2018: 11 · 2017: 13 · 2016: 22 · 2015: 20 · 2014: 27 · 2013: 27 · 2012: 21
- FWCI
- 11.04
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Research Publications (Maastricht University) (publishedVersion, cc-by-nc-sa)
- Research Publications (Maastricht University) (submittedVersion, other-oa)
- Funders
- European Commission
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Bipolar Disorder and Treatment
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Health Sciences › Medicine › Pharmacology (medical) › Treatment of Major Depression
- Keywords
- glycogen synthase kinase-3β, transgenic mice, hyperactivity, mania, bipolar disorder, lithium, AKT1, brain-derived neurotrophic factor, striatum, hippocampus, locomotor activity, acoustic startle response, habituation, ACTH, compensatory signaling, neuroplasticity
- MeSH terms
- Glycogen Synthase Kinase 3 beta, Adrenocorticotropic Hormone, Animals, Bipolar Disorder, Corticosterone, Disease Models, Animal, DNA, Drinking, Eating, Female, Hippocampus, Hyperkinesis, Male, Mice, Transgenic, Motor Activity, Reflex, Startle, Swimming, Signal Transduction, Photoperiod, Brain-Derived Neurotrophic Factor, Glycogen Synthase Kinase 3, Mice
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