title: Glycogen synthase kinase-3beta affects size of dentate gyrus and species-typical behavioral tasks in transgenic and knockout mice.
abstract: 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.
authors.affiliation: Laboratory of Neurobiology, Nencki Institute, Polish Academy of Sciences, 3 Pasteur St., 02-093 Warsaw, Poland.
authors.forename: Ilona
authors.initials: I
authors.lastname: Kondratiuk
authors.forename: Herman
authors.initials: H
authors.lastname: Devijver
authors.forename: Benoit
authors.initials: B
authors.lastname: Lechat
authors.forename: Fred
authors.initials: F
authors.lastname: Van Leuven
authors.forename: Leszek
authors.initials: L
authors.lastname: Kaczmarek
authors.forename: Robert K
authors.initials: RK
authors.lastname: Filipkowski
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000502:physiology*; D018891:Dentate Gyrus / Q000378:metabolism*; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism*; D000071679:Glycogen Synthase Kinase 3 beta; D006624:Hippocampus / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout / Q000378:metabolism*; D008822:Mice, Transgenic / Q000378:metabolism*; D055495:Neurogenesis / Q000502:physiology; D009474:Neurons / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology
chemical_list: D000071679:Glycogen Synthase Kinase 3 beta; C000605507:Gsk3b protein, mouse; D038362:Glycogen Synthase Kinase 3