2023 Fiscal Year Final Research Report
Single-cell Whole-transcriptome Analysis in Rat Basal Forebrain for Elucidating the Molecular Mechanism in Postoperative Delirium
| Project/Area Number |
21K16533
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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 55050:Anesthesiology-related
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| Research Institution | Tohoku University |
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Principal Investigator |
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| Project Period (FY) |
2021-04-01 – 2024-03-31
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| Keywords | せん妄 / 術後せん妄 / 遺伝子解析 / 前脳基底部 |
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| Outline of Final Research Achievements |
The pathogenesis of postoperative delirium remains unknown, and no effective preventive or curative treatment is available. To elucidate the molecular mechanism of postoperative delirium, we focused on the basal forebrain (BFB), which cholinergically projects to the cerebral cortex, thalamus, hippocampus, and hypothalamus, and examined the changes in BFB gene expression.
We observed that mice undergoing abdominal surgery under general anesthesia (group S), those under general anesthesia only (group A), and untreated mice (group N) exhibited delirium-like behavioral changes in the S and A groups compared with those in the N group in an elevated plus-maze behavioral experiment. mRNA was extracted from the BFB of the three groups and gene expression was analyzed. Notably, the expression of Chrna3, which encodes a central acetylcholine receptor distributed across the synapses, increased 5.3-fold in the BFB following delirium-like behavior (adjusted p < 0.001).
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| Free Research Field |
せん妄
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| Academic Significance and Societal Importance of the Research Achievements |
手術後せん妄は，入院期間の延長・認知機能障害の残存・死亡の増加に繋がる．もっとも研究されてきた仮説は海馬での炎症モデルであるが，分子レベルでの詳細な脳内機序は現在，ほとんど明らかになっていない．
本研究の独自的な点は， BFBに着目したことであり，BFBにおける遺伝子発現変化を観察した研究は皆無であった．本研究は，せん妄様行動を呈したマウスのBFBにおける全遺伝子発現量を観察した初の研究であり，147遺伝子の有意な発現変化を確認できた．
申請者は継続して研究を続けており，本研究が手術後の認知機能の維持および健康寿命の延長とともに，本邦の手術医療の長期成績の向上に繋がると確信している．
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