Development of a novel gene therapy on narcolepsy using AAV vectors and artificial GPCRs
| Project/Area Number |
23659134
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| Research Category |
Grant-in-Aid for Challenging Exploratory Research
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| Allocation Type | Multi-year Fund |
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| Research Field |
General pharmacology
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| Research Institution | Kanazawa University |
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Principal Investigator |
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| Co-Investigator(Renkei-kenkyūsha) |
SAKURAI Takeshi 金沢大学, 医学系, 教授 (60251055)
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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 |
¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
Fiscal Year 2013: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2012: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2011: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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| Keywords | 中枢・末梢神経 / 睡眠・覚醒 / オレキシン / ノルアドレナリン / セロトニン / ウィルスベクター / DREADD / マウス / ナルコレプシー / AAV / 遺伝子治療 / 睡眠･覚醒 |
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| Research Abstract |
The loss of orexin neurons in humans is associated with narcolepsy, a sleep disorder characterized by excessive daytime sleepiness and cataplexy. However, the precise neural mechanisms downstream of orexin neurons remain unknown.
We found that the locus coeruleus noradrenergic and dorsal raphe serotonergic neurons play differential roles in the regulation of sleep/wakefulness by orexin neurons: the former stabilizes wakefulness episodes (reduce sleepiness) and the latter suppresses cataplexy in mice. In addition, we developed a system to suppress narcolepsy in mice by artificially activating these neurons using recombinant AAV vectors and an artificial GPCR called DREADD.
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Report
(4 results)
Research Products
(32 results)
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[Presentation] Restoration of orexin signaling in the dorsal raphe and locus coeruleus differentially ameliorate symptoms of narcoleptic mice2013
Author(s)
Hasegawa, E., Yanagisawa, M., Roth, B.L., Sakurai, T., and Mieda, M
Organizer
The 5th World Congress on Sleep Medicine
Place of Presentation
Valencia, Spain
Year and Date
2013-09-28
Related Report
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[Presentation] Differential roles of orexin receptor-1 and -2 in the regulation of non-REM and REM sleep2011
Author(s)
Mieda, M., Hasegawa, E., Kisanuki, Y.Y., Sinton, C.M., Yanagisawa, M., and Sakurai, T
Organizer
Worldsleep2011 (World Federation of Sleep Research & Sleep Medicine Societies)
Place of Presentation
Kyoto
Related Report
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