| Project/Area Number |
24689039
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| Research Category |
Grant-in-Aid for Young Scientists (A)
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| Allocation Type | Partial Multi-year Fund |
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| Research Field |
Neurology
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| Research Institution | Tokyo Medical and Dental University |
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Principal Investigator |
OHKUBO TAKUYA 東京医科歯科大学, 医歯(薬)学総合研究科, 助教 (90587461)
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| Co-Investigator(Renkei-kenkyūsha) |
UCHIHARA Toshiki 公益財団法人東京都医学総合研究所, 東京都神経科学総合研究所, 副参事研究員 (10223570)
KIMURA Nobuyuki 国立長寿医療研究センター, 認知症先進医療開発センター, 室長 (80392330)
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| Project Period (FY) |
2012-04-01 – 2014-03-31
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| Project Status |
Completed (Fiscal Year 2013)
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| Budget Amount *help |
¥25,740,000 (Direct Cost: ¥19,800,000、Indirect Cost: ¥5,940,000)
Fiscal Year 2013: ¥12,090,000 (Direct Cost: ¥9,300,000、Indirect Cost: ¥2,790,000)
Fiscal Year 2012: ¥13,650,000 (Direct Cost: ¥10,500,000、Indirect Cost: ¥3,150,000)
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| Keywords | ALS / 霊長類モデル / TDP-43 / 経シナプス伝播 / AAVベクター / 伝播 / リン酸化 |
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| Research Abstract |
We succeeded in establishing the first non-human primate model of ALS by overexpression of wild-type human TDP-43 in the spinal cord of cynomolgus monkeys. The distribution of exogenous wild-type human TDP-43 in this model was represented not only at the anterior horn neurons injected side, but at those of the other side of the same spinal cord, at those injected side from the cervical to lumbar level and at Betz neurons in the precentral area of motor cortex.
To elucidate the pathomechanism of exogenous TDP-43 propagation in this model, we designed new constructs using pAAV-IRES-GFP vector, which could express both GFP and flag-tagged human TDP-43. Exogenous TDP-43 positive and GFP negative neurons were observed at more broad range of spinal cord than GFP positive and TDP-43 negative neurons. These data might indicate that TDP-43 could propagate along the same column (intracolumn spread), among different columns (intercolumn spread) and neighboring cells (local cell-to-cell spread).
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