Abnormalities in brain structure and behavior in GSK-3alpha mutant mice Academic Article uri icon

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abstract

  • BACKGROUND: Glycogen synthase kinase-3 (GSK-3) is a widely expressed and highly conserved serine/threonine protein kinase encoded by two genes that generate two related proteins: GSK-3alpha and GSK-3beta. Mice lacking a functional GSK-3alpha gene were engineered in our laboratory; they are viable and display insulin sensitivity. In this study, we have characterized brain functions of GSK-3alpha KO mice by using a well-established battery of behavioral tests together with neurochemical and neuroanatomical analysis. RESULTS: Similar to the previously described behaviours of GSK-3beta(+/-) mice, GSK-3alpha mutants display decreased exploratory activity, decreased immobility time and reduced aggressive behavior. However, genetic inactivation of the GSK-3alpha gene was associated with: decreased locomotion and impaired motor coordination, increased grooming activity, loss of social motivation and novelty; enhanced sensorimotor gating and impaired associated memory and coordination. GSK-3alpha KO mice exhibited a deficit in fear conditioning, however memory formation as assessed by a passive avoidance test was normal, suggesting that the animals are sensitized for active avoidance of a highly aversive stimulus in the fear-conditioning paradigm. Changes in cerebellar structure and function were observed in mutant mice along with a significant decrease of the number and size of Purkinje cells. CONCLUSION: Taken together, these data support a role for the GSK-3alpha gene in CNS functioning and possible involvement in the development of psychiatric disorders.

authors

  • Kaidanovich-Beilin, Oksana
  • Lipina, Tatiana V
  • Takao, Keizo
  • van Eede, Matthijs
  • Hattori, Satoko
  • Laliberté, Christine
  • Khan, Mustafa
  • Okamoto, Kenichi
  • Chambers, John W
  • Fletcher, Paul J
  • MacAulay, Katrina
  • Doble, Bradley
  • Henkelman, Mark
  • Miyakawa, Tsuyoshi
  • Roder, John
  • Woodgett, James R

publication date

  • 2009