| Project/Area Number |
18390260
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Neurology
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| Research Institution | The University of Tokushima |
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Principal Investigator |
KAJI Ryuji The University of Tokushima, Health Biosciences, Graduate School, MD, PhD. Professor (00214304)
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| Co-Investigator(Kenkyū-buntansha) |
GOTO Satoshi The University of Tokushima, Health Biosciences, Graduate School, MD, PhD.Visiting Professor (50240916)
TAMIYA Gen The University of Tokushima, Health Biosciences, Graduate School, PhD. Visiting Professor (10317745)
島津 秀紀 徳島大学, 大学院ヘルスバイオサイエンス研究部, 助手 (50398012)
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| Project Period (FY) |
2006 – 2007
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| Project Status |
Completed (Fiscal Year 2007)
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| Budget Amount *help |
¥17,200,000 (Direct Cost: ¥15,700,000、Indirect Cost: ¥1,500,000)
Fiscal Year 2007: ¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
Fiscal Year 2006: ¥10,700,000 (Direct Cost: ¥10,700,000)
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| Keywords | international cooperation / gene / genome / neurology / neunological disorder / DYT3 / ルーバッグ病 / TAF1 / 深部脳刺激法 / 大脳磁気刺激法 / 感覚運動連関 |
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| Research Abstract |
Dystonia is defined as a syndrome of abnormal muscle contraction frequently causing twisting or repetitive meovements. The number of dystonia patients in Japan has been estimated to be more than 20,000. Its cause and pathological findings were unknown. We conducted a research claryfing the pathomechanism and developing therapeutic means for dystonia using a multi-disciplinary approach including molecular genetics, histochemical, neurophysiological methods. We for the first time discovered the gene causing a hereditary dystonia, DYT3, and together with our previous pathological findings possibly explaining dystonia (Goto et al Ann Neurol 2005), we put forward a hypothesis on the genesis of dystonia: dystonia is a disorder of motor program (or subroutine) that defines sensory input versus motor output in semi-automatic tasks such as head turning, blinking, writing, playing musical instruments and others. This integration most likely involves cortico-striatal symapse at the putamen using LTP in the presence of dopamine. If the control of dopamine release is impaired by the dysfunction of striosome, there may be abnormal LTP-like neuroplasticity with impaired depotentiation, which leads to relative increase of dopamine release in the direct comp oared to indirect pathway in the matrix. The latter may cause abnormal LTP-like neuroplasticity leading to abnormal sensorimotor link in dystonia.
We also developed therapies using type B botulinum toxin injection, deep brain stimulation and repetitive transcranial magnetic stimulation.
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