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

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

Research output: Contribution to journalArticle

112 Citations (Scopus)

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-3 and GSK-3. Mice lacking a functional GSK-3 gene were engineered in our laboratory; they are viable and display insulin sensitivity. In this study, we have characterized brain functions of GSK-3 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-3+/-mice, GSK-3 mutants display decreased exploratory activity, decreased immobility time and reduced aggressive behavior. However, genetic inactivation of the GSK-3 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-3 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-3 gene in CNS functioning and possible involvement in the development of psychiatric disorders.

Original languageEnglish
Article number35
JournalMolecular Brain
Volume2
Issue number1
DOIs
Publication statusPublished - 28-12-2009

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Glycogen Synthase Kinase 3
Brain
Genes
Fear
glycogen synthase kinase 3 alpha
Sensory Gating
Grooming
Purkinje Cells
Protein-Serine-Threonine Kinases
Locomotion
Psychiatry
Insulin Resistance
Motivation

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Cellular and Molecular Neuroscience

Cite this

Kaidanovich-Beilin, O., Lipina, T. V., Takao, K., Van Eede, M., Takai, S., Laliberté, C., ... Woodgett, J. R. (2009). Abnormalities in brain structure and behavior in GSK-3alpha mutant mice. Molecular Brain, 2(1), [35]. https://doi.org/10.1186/1756-6606-2-35
Kaidanovich-Beilin, Oksana ; Lipina, Tatiana V. ; Takao, Keizo ; Van Eede, Matthijs ; Takai, Satoko ; Laliberté, Christine ; Khan, Mustafa ; Okamoto, Kenichi ; Chambers, John W. ; Fletcher, Paul J. ; MacAulay, Katrina ; Doble, Bradley W. ; Henkelman, Mark ; Miyakawa, Tsuyoshi ; Roder, John ; Woodgett, James R. / Abnormalities in brain structure and behavior in GSK-3alpha mutant mice. In: Molecular Brain. 2009 ; Vol. 2, No. 1.
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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-3 and GSK-3. Mice lacking a functional GSK-3 gene were engineered in our laboratory; they are viable and display insulin sensitivity. In this study, we have characterized brain functions of GSK-3 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-3+/-mice, GSK-3 mutants display decreased exploratory activity, decreased immobility time and reduced aggressive behavior. However, genetic inactivation of the GSK-3 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-3 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-3 gene in CNS functioning and possible involvement in the development of psychiatric disorders.",
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Kaidanovich-Beilin, O, Lipina, TV, Takao, K, Van Eede, M, Takai, S, Laliberté, C, Khan, M, Okamoto, K, Chambers, JW, Fletcher, PJ, MacAulay, K, Doble, BW, Henkelman, M, Miyakawa, T, Roder, J & Woodgett, JR 2009, 'Abnormalities in brain structure and behavior in GSK-3alpha mutant mice', Molecular Brain, vol. 2, no. 1, 35. https://doi.org/10.1186/1756-6606-2-35

Abnormalities in brain structure and behavior in GSK-3alpha mutant mice. / Kaidanovich-Beilin, Oksana; Lipina, Tatiana V.; Takao, Keizo; Van Eede, Matthijs; Takai, Satoko; Laliberté, Christine; Khan, Mustafa; Okamoto, Kenichi; Chambers, John W.; Fletcher, Paul J.; MacAulay, Katrina; Doble, Bradley W.; Henkelman, Mark; Miyakawa, Tsuyoshi; Roder, John; Woodgett, James R.

In: Molecular Brain, Vol. 2, No. 1, 35, 28.12.2009.

Research output: Contribution to journalArticle

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T1 - Abnormalities in brain structure and behavior in GSK-3alpha mutant mice

AU - Kaidanovich-Beilin, Oksana

AU - Lipina, Tatiana V.

AU - Takao, Keizo

AU - Van Eede, Matthijs

AU - Takai, Satoko

AU - Laliberté, Christine

AU - Khan, Mustafa

AU - Okamoto, Kenichi

AU - Chambers, John W.

AU - Fletcher, Paul J.

AU - MacAulay, Katrina

AU - Doble, Bradley W.

AU - Henkelman, Mark

AU - Miyakawa, Tsuyoshi

AU - Roder, John

AU - Woodgett, James R.

PY - 2009/12/28

Y1 - 2009/12/28

N2 - 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-3 and GSK-3. Mice lacking a functional GSK-3 gene were engineered in our laboratory; they are viable and display insulin sensitivity. In this study, we have characterized brain functions of GSK-3 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-3+/-mice, GSK-3 mutants display decreased exploratory activity, decreased immobility time and reduced aggressive behavior. However, genetic inactivation of the GSK-3 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-3 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-3 gene in CNS functioning and possible involvement in the development of psychiatric disorders.

AB - 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-3 and GSK-3. Mice lacking a functional GSK-3 gene were engineered in our laboratory; they are viable and display insulin sensitivity. In this study, we have characterized brain functions of GSK-3 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-3+/-mice, GSK-3 mutants display decreased exploratory activity, decreased immobility time and reduced aggressive behavior. However, genetic inactivation of the GSK-3 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-3 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-3 gene in CNS functioning and possible involvement in the development of psychiatric disorders.

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Kaidanovich-Beilin O, Lipina TV, Takao K, Van Eede M, Takai S, Laliberté C et al. Abnormalities in brain structure and behavior in GSK-3alpha mutant mice. Molecular Brain. 2009 Dec 28;2(1). 35. https://doi.org/10.1186/1756-6606-2-35