A new model of attention deficit/hyperactivity disorder (ADHD) related with Arcadlin
| Project/Area Number |
17K10064
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Pediatrics
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| Research Institution | Tokyo Women's Medical University |
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Principal Investigator |
Takemiya Takako 東京女子医科大学, 看護学部, 准教授 (70297547)
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| Co-Investigator(Kenkyū-buntansha) |
安田 新 公益財団法人東京都医学総合研究所, 脳発達・神経再生研究分野, 研究員 (20392368)
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| Project Period (FY) |
2017-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2019: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
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| Keywords | Arcadlin / 注意欠如多動性障害(ADHD) / 多動性 / 衝動性 / 扁桃体 / スパイン密度 / 線条体 / 注意欠如 / 注意欠如多動性障害 / 動物 / 神経科学 / 脳神経疾患 |
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| Outline of Final Research Achievements |
Attention deficit/hyperactivity disorder (ADHD) is characterized by hyperactivity, impaired sustained attention, impulsivity, and learning disability concerning with dopamine in prefrontal cortex. Reduction of neuronal excitability via NMDA receptor antagonism is associated with impulsivity and hyperactivity. Arcadlin is induced in neurons by NMDA dependent synaptic activity.
We hypothesized that inhibition of Arcadlin was related with the mechanisms of NMDA inhibiting ADHD and investigated whether arcadlin knockout mice (ko) revealed ADHD like behavior.
Hyperactivity and impulsivity was found in ko. The size of striatum and whole brain was significantly small in ko, which is also reported in ADHD children. In addition, ko kept working memory and spatial learning and memory, suggesting there is no learning disorder concerning with the function of prefrontal cortex and hippocampus in ko. Therefore, inhibition of Arcadlin showed ADHD and might be the mechanism of NMDA-blocking ADHD.
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| Academic Significance and Societal Importance of the Research Achievements |
ADHDは衝動性、注意欠如、多動を特徴とする発達性の行動障害である。治療薬としてメチルフェニデート(MPH)が使われ、ADHDの発生機序にドパミン異常が関係すると考えられている。しかし、ADHDの20～30％にはMPHの効果がなくドパミン以外の機序の存在が示唆されていた。本研究成果から、細胞接着分子のプロトカドヘリンarcadlin/PCDH8（Arcadlin）の欠損がドパミン系とは異なる機序でADHDの発生に関わることが推察された。本成果はADHD発生機序解明および新しい治療戦略の糸口として、その社会的意義は大きい。
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Report
(4 results)
Research Products
(11 results)
