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 18F-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.
Keywords: Alzheimer's disease, brain metabolism, deoxyglucose, glycogen synthase kinase-3β, PET, transgenic mouse.
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