Glycogen synthase kinase-3beta affects size of dentate gyrus and species-typical behavioral tasks in transgenic and knockout mice

Behav Brain Res. 2013 Jul 1;248:46-50. doi: 10.1016/j.bbr.2013.03.045. Epub 2013 Apr 6.


Glycogen synthase kinase-3 (GSK-3), a multifunctional serine-threonine kinase, is an important regulator in numerous signaling pathways and processes including adult brain neurogenesis. GSK-3 (mal)functioning was implicated in many diseases, in particular neurological and behavioral disorders. We investigated the impact of altered levels of the GSK-3β isoform on hippocampal size, number of doublecortin-positive cells, and hippocampal-dependent behaviors. Both GSK-3β transgenic mice (GSK-3β[S9A] mice) and GSK-3β neuron-specific knockout (GSK-3β(n-/-)) mice, showed reduced size of the dentate gyrus (DG) and were impaired in three hippocampal-dependent, species-typical behavioral tasks: digging, marble burying and nest building. We further demonstrate that the number of differentiating, doublecortin-positive new neurons is reduced in GSK-3β[S9A] mice, but not in GSK-3β(n-/-) mice. We conclude that GSK-3β activity must be critically controlled to allow wild type-like volume of the dentate gyrus and for normal execution of hippocampal-dependent, species-typical behavior.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Behavior, Animal / physiology*
  • Dentate Gyrus / metabolism*
  • Glycogen Synthase Kinase 3 / metabolism*
  • Glycogen Synthase Kinase 3 beta
  • Hippocampus / metabolism*
  • Mice
  • Mice, Knockout / metabolism*
  • Mice, Transgenic / metabolism*
  • Neurogenesis / physiology
  • Neurons / metabolism
  • Signal Transduction / physiology


  • Glycogen Synthase Kinase 3 beta
  • Gsk3b protein, mouse
  • Glycogen Synthase Kinase 3