| Project/Area Number |
25430061
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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 |
Neurochemistry/Neuropharmacology
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| Research Institution | Gunma University |
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Principal Investigator |
Sadakata Tetsushi 群馬大学, テニュアトラック普及推進室, 講師 (90391961)
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| Project Period (FY) |
2013-04-01 – 2017-03-31
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| Project Status |
Completed (Fiscal Year 2016)
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| Budget Amount *help |
¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2015: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2014: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2013: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
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| Keywords | Tremor / 振戦 / ARF / trafficking / tremor |
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| Outline of Final Research Achievements |
ADP-ribosylation factors (ARFs) constitute a family of small monomeric GTPases. The ARF family consists of three classes and a total of six members: class I, consisting of ARFs 1-3; class II, consisting of ARFs 4 and 5; and class III, which comprises ARF6. Little is known about the role of the class II ARFs in membrane trafficking. Here, we generated class II ARF knockout mice, and found that ARF4+/-/ARF5-/- mice showed severe tremor. Propranolol and gabapentin, which alleviate symptoms in essential tremor patients, reduced the amplitude of the pathologic tremor. Immunochemical studies showed that Nav1.6 proteins, normally localized in axon initial segment (AIS), was highly decreased in ARF4+/-/ARF5-/- Purkinje cell. These results indicate that the impairment of electrophysiological properties of Purkinje cell by Nav1.6 decrease is related to the onset of pathologic tremor of essential tremor patients.
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