抄録
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.
| 元の言語 | English |
|---|---|
| 記事番号 | 35 |
| ジャーナル | Molecular Brain |
| 巻 | 2 |
| 発行部数 | 1 |
| DOI | |
| 出版物ステータス | Published - 28-12-2009 |
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All Science Journal Classification (ASJC) codes
- Molecular Biology
- Cellular and Molecular Neuroscience
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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.
：: Molecular Brain, 巻 2, 番号 1, 35, 28.12.2009.研究成果: Article
TY - JOUR
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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U2 - 10.1186/1756-6606-2-35
DO - 10.1186/1756-6606-2-35
M3 - Article
C2 - 19925672
AN - SCOPUS:72449146342
VL - 2
JO - Molecular Brain
JF - Molecular Brain
SN - 1756-6606
IS - 1
M1 - 35
ER -