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

Research output: Contribution to journalJournal articleResearchpeer-review

  • K Spittaels
  • C Van den Haute
  • J Van Dorpe
  • D Terwel
  • K Vandezande
  • R Lasrado
  • K Bruynseels
  • M Irizarry
  • M Verhoye
  • J Van Lint
  • J R Vandenheede
  • D Ashton
  • M Mercken
  • Loos, Ruth
  • B Hyman
  • A Van der Linden
  • H Geerts
  • F Van Leuven

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.

Original languageEnglish
JournalNeuroscience
Volume113
Issue number4
Pages (from-to)797-808
Number of pages12
ISSN0306-4522
DOIs
Publication statusPublished - 2002
Externally publishedYes

    Research areas

  • Animals, Animals, Newborn, Brain/enzymology, Female, Glycogen Synthase Kinase 3/biosynthesis, Humans, Male, Mice, Mice, Inbred C57BL, Mice, Transgenic, Neurons/enzymology, Psychomotor Performance/physiology

ID: 258333362