| Project/Area Number |
18K14832
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 46010:Neuroscience-general-related
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| Research Institution | Tokyo Metropolitan Institute of Medical Science |
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Principal Investigator |
HIRAI Shinobu 公益財団法人東京都医学総合研究所, 精神行動医学研究分野, 主任研究員 (00625189)
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| Project Period (FY) |
2018-04-01 – 2022-03-31
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| Project Status |
Completed (Fiscal Year 2021)
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| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2020: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2019: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2018: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
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| Keywords | 糖代謝 / 精神疾患 / 血管障害 / グリア / 抑制性ニューロン / PVニューロン / アストロサイト / ミクログリア / 統合失調症 / 双極性障害 / 砂糖 / 思春期 / 環境要因 / グリア細胞 / 毛細血管障害 / 砂糖過多 / 栄養 / 炎症 / 食事環境 |
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| Outline of Final Research Achievements |
By combining the mice having a susceptibility gene for psychiatric disorder with environmental factors of excessive sugar intake at the age of puberty, we successfully created a novel mouse model exhibiting various mental disorder-like symptoms. In other words, this demonstrates a possibility that the excessive intake of simple sugar at the age of puberty could be an environmental risk factor of psychiatric disorders.
Furthermore, we found “cerebral microvascular angiopathy” that was accompanied by an impaired glucose incorporation in our model mice. In order to verify the generality of this finding, we used a post-mortem brain from patients with SZ and BD, and identified angiopathy similar to the one seen in the model mice. These phenotypes were prevented by continuous administration of non-steroidal anti-inflammatory drugs (NSAIDs) before the onset of the disease, and some psychiatric-like symptoms were also suppressed.
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| Academic Significance and Societal Importance of the Research Achievements |
統合失調症や双極性障害は、若年発症の難治性慢性疾患で発症メカニズムが不明のため、予防法、治療法が確立していません。様々な遺伝的要因のほか、環境要因も想定されていますが、脳機能を障害する確固たる原因は未だ同定されておらず、予防、治療法の確立が強く望まれています。
本研究成果は、精神疾患発症の背景に血管の障害による栄養素の取り込み低下といった代謝障害が潜在的に存在する可能性を示唆しており、今後、既存の神経伝達物質の受容体やトランスポータに対する創薬だけでなく、代謝制御といった新たな観点からの予防、治療法の開発が見込まれます。
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