AmuIti-disciplinary approach to the genesis and therapy for dystonia

肌张力障碍的起源和治疗的多学科方法

• 批准号: 18390260
• 负责人: KAJI Ryuji
• 金额: $ 11.01万
• 依托单位: The University of Tokushima
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2006
• 资助国家: 日本
• 起止时间: 2006 至 2007
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-18390260/
• 关键词: 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

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.

肌张力障碍被定义为异常肌肉收缩的综合征，经常引起扭曲或重复的大力作用。日本的肌张力障碍患者数量估计超过20,000。它的原因和病理发现尚不清楚。我们使用多学科方法（包括分子遗传学，组织化学，神经生理学方法）进行了一项研究，该研究结论了致病机制和开发肌张力障碍的治疗手段。 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,写作，演奏乐器等。这种整合最有可能涉及在多巴胺存在下使用LTP在壳虫下的皮质 - 纹状体对称。如果释放功能障碍会损害多巴胺释放的控制，则可能存在异常的LTP神经可塑性，而寄生虫受损，这会导致在基质中直接增加到间接途径的多巴胺释放的相对增加。后者可能引起异常LTP样神经塑性，导致肌张力障碍中异常的感觉运动链接。我们还使用B型肉毒杆菌毒素注射，深脑刺激和重复的经颅磁刺激开发了疗法。

项目成果

Modulation of torsinA expression in the globus pallidus internus is associated with levodopa-induced dyskinesia in hemiparkinsonian rats.

苍白球内部 torsinA 表达的调节与偏侧帕金森病大鼠中左旋多巴诱导的运动障碍有关。

• 发表时间: 2006
• 期刊: Neurosci Lett 396(1)
• 作者: Taro Hino;Takashi Kanda;TetsuyaTerasaki;他(8;9 番目);Jun-ichi Sato;神田 隆;古賀道明;佐野泰照;清水文崇;前田敏彦;Sato K;神田 隆;Makino S;清水文崇;Yamada K
• 通讯作者: Yamada K

Abnormal sensorimotor integration in hand dystonia.

手部肌张力障碍的感觉运动整合异常。

• 发表时间: 2006
• 期刊: Suppl Clin Neurophysiol 59
• 作者: Taro Hino;Takashi Kanda;TetsuyaTerasaki;他(8;9 番目);Jun-ichi Sato;神田 隆;古賀道明;佐野泰照;清水文崇;前田敏彦;Sato K;神田 隆;Makino S;清水文崇;Yamada K;Urushihara R;神田 隆;Murase N
• 通讯作者: Murase N

Effect of repetitive transcranial magnetic stimulation applied over the promotor cortex on somatosensory-evoked potentials and regional cerebral blood flow.

对启动子皮质施加重复经颅磁刺激对体感诱发电位和局部脑血流的影响。

• 发表时间: 2006
• 期刊: Neuroimage 31(2)
• 作者: Taro Hino;Takashi Kanda;TetsuyaTerasaki;他(8;9 番目);Jun-ichi Sato;神田 隆;古賀道明;佐野泰照;清水文崇;前田敏彦;Sato K;神田 隆;Makino S;清水文崇;Yamada K;Urushihara R
• 通讯作者: Urushihara R