Abnormalities in brain structure and behavior in GSK-3alpha mutant mice

Mol Brain. 2009 Nov 19;2:35. doi: 10.1186/1756-6606-2-35.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aggression / physiology
  • Animals
  • Behavior, Animal*
  • Brain / abnormalities*
  • Brain / enzymology*
  • Brain / pathology
  • Brain / physiopathology
  • Depression / pathology
  • Depression / physiopathology
  • Emotions
  • Female
  • Glycogen Synthase Kinase 3 / deficiency
  • Glycogen Synthase Kinase 3 / metabolism*
  • Magnetic Resonance Imaging
  • Memory, Long-Term / physiology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mice, Neurologic Mutants
  • Neurotransmitter Agents / metabolism
  • Social Behavior

Substances

  • Neurotransmitter Agents
  • Glycogen Synthase Kinase 3
  • glycogen synthase kinase 3 alpha