| Project/Area Number |
23591265
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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 |
Neurology
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| Research Institution | Department of Clinical Research, National Hospital Organization Utano National Hospital |
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Principal Investigator |
KENJI Yamamoto 独立行政法人国立病院機構(宇多野病院臨床研究部), その他部局等, 研究員 (50378775)
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| Co-Investigator(Kenkyū-buntansha) |
SAWADA Hideyuki 独立行政法人国立病院機構, 宇多野病院臨床研究部, 臨床研究部長 (30335260)
YAMAKAWA Kentaro 独立行政法人国立病院機構, 宇多野病院臨床研究部, 研究員 (70447960)
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| Project Period (FY) |
2011 – 2013
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| Project Status |
Completed (Fiscal Year 2013)
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| Budget Amount *help |
¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000)
Fiscal Year 2013: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2012: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2011: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
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| Keywords | αシヌクレイン / オリゴマー / パーキンソン病 / レビー小体型認知症 / カリウムチャンネル / カルシウム / 膜興奮性 / パッチクランプ / ドーパミン / 神経変性 / シナプス伝達 |
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| Research Abstract |
We examined the action of alpha-synuclein oligomers on neuronal excitabilities by injecting protein into pyramidal neurons in mouse cortical slices through whole-cell patch pipettes.
Western blot analysis showed that the pipette solution including alpha-synuclein incubated with dopamine (aS+DA), had higher order oligomer. Intracellular application of aS+DA suppressed spike firing during current injection. Nimodipine and apamin blocked the effect of aS+DA on spike firing. aS+DA prolonged the duration of spike afterhyperpolarization (AHP) and increased the charge transfer carried by the current during AHP under current clamp, both of which were inhibited by apamin.
These results suggest that alpha-synuclein oligomers suppress spike frequency by enhancing AHP, and apamin-sensitive SK-type calcium-activated potassium channel is involved with the enhancement. This mechanism may cause the downregulation of neocortical activities in Parkinson's disease and dementia with Lewy bodies.
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