Transgenic Mice Overexpressing Glycogen Synthase Kinase 3β: A Putative Model of Hyperactivity and Mania
| Autor: | Ilse Goris, Hansfried Van Craenendonck, Guy Daneels, Dieder Moechars, Ilse Lenaerts, J. Adriaan Bouwknecht, Thomas Steckler, Kim Cryns, Jos Prickaerts |
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| Přispěvatelé: | Psychiatrie en Neuropsychologie, Neuropsychology & Psychopharmacology, RS: FPN NPPP II |
| Rok vydání: | 2006 |
| Předmět: |
Male
Reflex Startle medicine.medical_specialty Bipolar Disorder Photoperiod Transgene Drinking Mice Transgenic Stimulation Hyperkinesis Motor Activity Hippocampus Eating Glycogen Synthase Kinase 3 Mice Adrenocorticotropic Hormone GSK-3 Neurotrophic factors Internal medicine medicine Animals Habituation GSK3B Swimming Brain-derived neurotrophic factor Glycogen Synthase Kinase 3 beta Chemistry Brain-Derived Neurotrophic Factor General Neuroscience Articles DNA Disease Models Animal Somatodendritic compartment Endocrinology Female Corticosterone Signal Transduction |
| Zdroj: | Journal of Neuroscience, 26, 9022-9. Society for Neuroscience |
| ISSN: | 1529-2401 0270-6474 |
| DOI: | 10.1523/jneurosci.5216-05.2006 |
| Popis: | Lithium is used as treatment for bipolar disorder with particular efficacy in the treatment of mania. Lithium inhibits glycogen synthase kinase 3 beta(GSK-3 beta) directly or indirectly via stimulation of the kinase Akt-1. We therefore investigated the possibility that transgenic mice overexpressing GSK-3 beta 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-3 beta by dimming the endogenous GSK-3 beta 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-3 beta, 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. |
| Databáze: | OpenAIRE |
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