title: A longitudinal FDG-PET study of transgenic mice overexpressing GSK- 3β in the brain.
abstract: Increased Glycogen synthase kinase-3 (GSK-3) activity is believed to contribute to the etiology of chronic disorders such as Alzheimer's disease, one of the earliest diseases linked to GSK-3 dysfunction. Numerous mouse models with modified GSK-3 have been generated in order to study the physiology of GSK-3, its implication in diverse pathologies and the potential effect of GSK-3 inhibitors. In this study we have characterised and evaluated the brain metabolic changes induced by GSK-3β overexpression in transgenic mice throughout their lifespan. The conditional Tet/GSK-3β transgenic line used in this study has been previously extensively characterized at the pathological, biochemical and cognitive levels. Now we have investigated the effect GSK-3β overexpression on the (18)F-fluoro-deoxyglucose (FDG) uptake by positron emission tomography (PET), taking advantage from this non-invasive technique which has allowed us to track individually the same animals throughout their lives. The results obtained during the longitudinal analysis showed a reduction of metabolic activity in several brain regions, such as cortex, striatum and hippocampus, consistent with the areas where the transgene is being expressed. The reduction of the metabolic activity in these mice is observed from the first time point, performed at the age of 3 months, and maintained throughout the whole study, until the oldest age tested (19 months). This effect seems to be reverted in a satellite group of 3-month transgenic animals treated with the classical GSK-3 inhibitor lithium, as they show higher FDG uptake values compared with untreated age-matched transgenic animals.
authors.forename: Javier
authors.initials: J
authors.lastname: de Cristóbal
authors.forename: Luis
authors.initials: L
authors.lastname: Garcia-Garcia
authors.forename: Mercedes
authors.initials: M
authors.lastname: Delgado
authors.forename: Miguel A
authors.initials: MA
authors.lastname: Pozo
authors.affiliation: CAI de Cartografia Cerebral, Instituto Pluridisciplinar, Universidad Complutense de Madrid, Paseo Juan XXIII 1, 28040 Madrid, Spain. jcristob@ucm.es.
authors.forename: Miguel
authors.initials: M
authors.lastname: Medina
mesh_terms: D000818:Animals; D001921:Brain / Q000000981:diagnostic imaging* / Q000201:enzymology*; D019788:Fluorodeoxyglucose F18; D015971:Gene Expression Regulation, Enzymologic; D038362:Glycogen Synthase Kinase 3 / Q000096:biosynthesis*; D000071679:Glycogen Synthase Kinase 3 beta; D008137:Longitudinal Studies; D051379:Mice; D008822:Mice, Transgenic; D009422:Nervous System Diseases / Q000000981:diagnostic imaging / Q000201:enzymology; D049268:Positron-Emission Tomography / Q000639:trends
chemical_list: D019788:Fluorodeoxyglucose F18; D000071679:Glycogen Synthase Kinase 3 beta; C000605507:Gsk3b protein, mouse; D038362:Glycogen Synthase Kinase 3