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Abnormalities in brain structure and behavior in GSK-3alpha mutant mice
- Source :
- Molecular Brain, Vol 2, Iss 1, p 35 (2009), Molecular Brain
- Publication Year :
- 2009
- Publisher :
- BMC, 2009.
-
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-3α and GSK-3β. Mice lacking a functional GSK-3α gene were engineered in our laboratory; they are viable and display insulin sensitivity. In this study, we have characterized brain functions of GSK-3α 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-3β+/-mice, GSK-3α mutants display decreased exploratory activity, decreased immobility time and reduced aggressive behavior. However, genetic inactivation of the GSK-3α 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-3α 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-3α gene in CNS functioning and possible involvement in the development of psychiatric disorders.
- Subjects :
- Memory, Long-Term
Emotions
Mutant
macromolecular substances
Biology
lcsh:RC346-429
Serine
Glycogen Synthase Kinase 3
Mice
Mice, Neurologic Mutants
03 medical and health sciences
Cellular and Molecular Neuroscience
0302 clinical medicine
Neurochemical
GSK-3
Animals
Threonine
Social Behavior
Glycogen synthase
Protein kinase A
Gene
Molecular Biology
lcsh:Neurology. Diseases of the nervous system
030304 developmental biology
Mice, Knockout
Neurotransmitter Agents
0303 health sciences
Behavior, Animal
Depression
Research
Brain
Magnetic Resonance Imaging
Cell biology
Aggression
Mice, Inbred C57BL
biology.protein
Female
Neuroscience
030217 neurology & neurosurgery
Subjects
Details
- Language :
- English
- ISSN :
- 17566606
- Volume :
- 2
- Issue :
- 1
- Database :
- OpenAIRE
- Journal :
- Molecular Brain
- Accession number :
- edsair.doi.dedup.....71a52c0fb92cd018ae0398bc6cfc4d01