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Experimental Genetics Group

Bolleke Abstract   Pijltje
Neonatal neuronal overexpression of glycogen synthase kinase-3 beta reduces brain size in transgenic mice.

Neuroscience. 2002;113(4):797-808.

Spittaels K1,7, Van den Haute C1,7, Van Dorpe J1, Terwel D1, Vandezande K1, Lasrado R1, Bruynseels K1, Irizarry M2, Verhoye M3, Van Lint J4, Vandenheede JR4, Ashton D5, Mercken M5, Loos R6, Hyman B2, Van der Linden A3, Geerts H5, Van Leuven F1.

1Experimental genetics Group, Department of Human Genetics, K.U.Leuven, Leuven, Belgium.
2Alzheimer Disease Research Unit, Massachusetts General Hospital-East, Charlestown, Massachusetts.
3Bio-Imaging Lab, Department of Physics, University of antwerp, Antwerp, Belgium.
4Department of Biochemistry, K.U.Leuven, Leuven, Belgium.
5Janssen Research Foundation, Beerse, Belgium
6Genetic Epidemiology, Department of Human Genetics, K.U.Leuven, Leuven, Belgium.
7These authors contributed equally to this work.

Glycogen synthase kinase-3beta (GSK-3beta) is important in neurogenesis. Here we demonstrate that the kinase influenced post-natal maturation and differentiation of neurons in vivo in transgenic mice that overexpress a constitutively active GSK-3beta[S9A]. Magnetic resonance imaging revealed a reduced volume of the entire brain, concordant with a nearly 20% reduction in wet brain weight. The reduced volume was most prominent for the cerebral cortex, without however, disturbing the normal cortical layering. The resulting compacted architecture was further demonstrated by an increased neuronal density, by reduced size of neuronal cell bodies and of the somatodendritic compartment of pyramidal neurons in the cortex. No evidence for apoptosis was obtained. The marked overall reduction in the level of the microtubule-associated protein 2 in brain and in spinal cord, did not affect the ultrastructure of the microtubular cytoskeleton in the proximal apical dendrites. The overall reduction in size of the entire CNS induced by constitutive active GSK-3beta caused only very subtle changes in the psychomotoric ability of adult and ageing GSK-3beta transgenic mice.

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