Investigation on the pathomechanism of autism spectrum disorder associated with hyperactivated mTOR signaling pathway
| Project/Area Number |
26860836
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Pediatrics
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| Research Institution | The University of Tokyo (2015-2016)
Tokyo Metropolitan Institute of Medical Science (2014) |
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Principal Investigator |
Atsushi Sato 東京大学, 医学部附属病院, 助教 (60466745)
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| Co-Investigator(Renkei-kenkyūsha) |
KOBAYASHI Toshiyuki 順天堂大学, 大学院医学研究科・分子病理病態学, 准教授 (40260070)
IKEDA Kazutaka 東京都医学総合研究所, 依存性薬物プロジェクト, 参事研究員 (60281656)
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| Research Collaborator |
KASHII Hirofumi
TANAKA Miho
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| Project Period (FY) |
2014-04-01 – 2017-03-31
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| Project Status |
Completed (Fiscal Year 2016)
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| Budget Amount *help |
¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
Fiscal Year 2016: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2015: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2014: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
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| Keywords | 自閉スペクトラム症 / 結節性硬化症 / mTOR / モデルマウス / 行動薬理学 / ｍTOR / 自閉症スペクトラム障害 |
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| Outline of Final Research Achievements |
We compared autism-related behavioral deficits in mouse models of tuberous sclerosis complex (TSC) caused by haploinsufficiency of TSC1 and TSC2. The mice with Tsc2 mutations showed severer autism-related behavior though mTOR-mediated signaling was equally hyperactivated at the protein level. Rapamycin, the mTOR inhibitor, normalized autism-related behavior and hyperactivated mTOR signaling in the mutant mice. エーs opposed to the earlier research, CDPPB (positivｅ allosteric modulator of metabotropic glutamate receptor 5, mGluR5) was ineffective for behavioral deficits in the mutant mice. MPEP (negative allosteric modulator of mGluR5) rather improved the autism-related behavior in the mutant mice.
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Report
(4 results)
Research Products
(26 results)
