2002 Fiscal Year Final Research Report Summary
Studies on signal transduction system in absence seizures
| Project/Area Number |
13672307
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Biological pharmacy
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| Research Institution | Nihon University |
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Principal Investigator |
ISHIGE Kumiko College of Pharmacy Full-time lecturer, 薬学部, 講師 (40212873)
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| Project Period (FY) |
2001 – 2002
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| Keywords | CREB / GHB model / lethargic mice / CBP / ATF 6 / ER stress / GRP 78 |
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| Research Abstract |
In this study, I examined the signal transduction pathway associated with activation of cyclic AMP responsive element binding protein (CREB), a transcription factor, in generalized absence seizures. In γ-hydroxybutylic acid (GHB) model mice, a drug-induced model, and lethargic (lh/lh) mice, a genetic model, CRE-binding activities in the cerebral cortex and thalamus were significantly higher than those in each control mice. These increases were not observed in the hippocampus or cerebellum in both model mice. Western blot analysis revealed that phosphoCREB (pCREB) but not CREB immunoreactivities in the cerebral cortex and thalamus in both model mice were higher than in each control mice, whereas there were no difference between the two in the hippocampus and cerebellum. CREB binding protein (CBP) immunoreactivities in the cerebral cortex and thalamus in the lethargic (lh/lh) mice were higher than those in control mice. The activating transcription factor (ATF6), a member of CREB/ATF family and an endoplasmic reticulum (ER) stress-induced transcription factor, immunoreactivity in the thalamus in lethargic (lh/lh) mice was lower than that in control mice. In addition, thalamic glucose-regulated protein 78 (GRP78) immunoreactivity in lethargic (lh/lh) mice was significantly lower than that in control mice. These data revealed that the increased CRE-binding activity was attributable to activation of the binding activity of pCREB and that lethargic (lh/lh) mice but not GHB model received ER stress accompanied with absence seizures.
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