| Project/Area Number |
24590653
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Applied pharmacology
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| Research Institution | Tohoku University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
福永 浩司 東北大学, 大学院薬学研究科, 教授 (90136721)
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| Project Period (FY) |
2012-04-01 – 2015-03-31
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| Project Status |
Completed (Fiscal Year 2014)
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| Budget Amount *help |
¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
Fiscal Year 2014: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2013: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2012: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
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| Keywords | ST101 / T-type CGCCs / CaMKII / OBX mice / アルツハイマー病 / 記憶学習 / CaM kinase II / T-type VGCC / 認知機能改善効果 / CaMキナーゼII / T型VGCC / 認知機能調節 / whole-cell patch-clamp法 |
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| Outline of Final Research Achievements |
We developed a novel cognitive enhancer, ST101 that activates T-type voltage-gated calcium channels (VGCCs). Here, we address whether T-type VGCC activation with ST101 mediates its cognitive effects in vivo and the relevance of T-type VGCC activation to acetylcholine release in the hippocampus. Acute administration of ST101 at 1 mg/kg, i.p. improved memory-related behaviors in olfactory bulbectomized (OBX) mice. Effects of ST101 administration were abolished by pre-administration of the T-type VGCC inhibitor mibefradil. As expected, significantly reduced CaMKIIα, PKCα, and ERK phosphorylation was restored by acute ST101 administration in the OBX mouse hippocampal CA1 region. Enhancement of CaMKIIα and PKCα but not ERK phosphorylation was inhibited by mibefradil. Taken together, stimulation of T-type VGCCs is critical for the enhanced hippocampal ACh release and improved cognitive function seen following ST101 administration.
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