title: GSK-3beta is required for memory reconsolidation in adult brain.
abstract: Activation of GSK-3beta is presumed to be involved in various neurodegenerative diseases, including Alzheimer's disease (AD), which is characterized by memory disturbances during early stages of the disease. The normal function of GSK-3beta in adult brain is not well understood. Here, we analyzed the ability of heterozygote GSK-3beta knockout (GSK+/-) mice to form memories. In the Morris water maze (MWM), learning and memory performance of GSK+/- mice was no different from that of wild-type (WT) mice for the first 3 days of training. With continued learning on subsequent days, however, retrograde amnesia was induced in GSK+/- mice, suggesting that GSK+/- mice might be impaired in their ability to form long-term memories. In contextual fear conditioning (CFC), context memory was normally consolidated in GSK+/- mice, but once the original memory was reactivated, they showed reduced freezing, suggesting that GSK+/- mice had impaired memory reconsolidation. Biochemical analysis showed that GSK-3beta was activated after memory reactivation in WT mice. Intraperitoneal injection of a GSK-3 inhibitor before memory reactivation impaired memory reconsolidation in WT mice. These results suggest that memory reconsolidation requires activation of GSK-3beta in the adult brain.
authors.affiliation: Lab for Alzheimer's Disease, RIKEN Brain Science Institute, Wako, Saitama, Japan.
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Kimura
authors.forename: Shunji
authors.initials: S
authors.lastname: Yamashita
authors.forename: Shinobu
authors.initials: S
authors.lastname: Nakao
authors.forename: Jung-Mi
authors.initials: JM
authors.lastname: Park
authors.forename: Miyuki
authors.initials: M
authors.lastname: Murayama
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Mizoroki
authors.forename: Yuji
authors.initials: Y
authors.lastname: Yoshiike
authors.forename: Naruhiko
authors.initials: N
authors.lastname: Sahara
authors.forename: Akihiko
authors.initials: A
authors.lastname: Takashima
mesh_terms: D000648:Amnesia, Retrograde / Q000235:genetics; D000818:Animals; D001921:Brain / Q000378:metabolism / Q000503:physiopathology*; D004789:Enzyme Activation / Q000235:genetics; D038362:Glycogen Synthase Kinase 3 / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D000071679:Glycogen Synthase Kinase 3 beta; D006579:Heterozygote; D008297:Male; D018782:Maze Learning / Q000502:physiology; D008568:Memory / Q000502:physiology*; D008569:Memory Disorders / Q000235:genetics* / Q000503:physiopathology / Q000534:rehabilitation*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010805:Physical Conditioning, Animal / Q000379:methods
chemical_list: D000071679:Glycogen Synthase Kinase 3 beta; C000605507:Gsk3b protein, mouse; D038362:Glycogen Synthase Kinase 3