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ケールの長期摂取が老化促進マウスSAMP8の認知機能に及ぼす影響

久志本, 尚子 信州大学

2020.10.26

概要

地球規模での高齢化は深刻な社会問題であり、加齢に伴う認知機能低下は人々のQOL(Quality of life)を著しく低下させる。脳の老化の特徴として、神経伝達障害、炎症、およびエネルギー代謝障害などが提唱されている。脳海馬は、認知機能に重要な役割を果たすが老化の影響を受けやすく、特に加齢に伴うシナプス可塑性障害は認知機能を著しく損なう。抗老化手段としては、適度な運動やカロリー制限とともに食品機能性成分の有効性が示されており、クルクミンやカテキンによる認知機能改善効果などが報告されている。ケール(Brassica oleracea L. var. acephala)は、栄養素に富み、青汁の原材料としてよく用いられるアブラナ科野菜である。その機能性についても、抗酸化作用や抗がん作用などが報告されているが、認知機能改善効果に関する知見はほとんど得られていない。そこで本研究では、ケールの長期摂取が老化促進マウスSAMP8(Senescence-accelerated mouse prone 8)の認知機能に及ぼす影響について検討した。

 本論文は全4章からなり、第1章では研究の背景および目的について述べている。続く第2章では、ケールの長期摂取が認知機能に及ぼす影響を検討した。SAMP8を2群に群分けし、コントロール群にはMF飼料(通常食)を、ケール搾汁(KJ : Kale juice)粉末摂取群には0.8%(w/w)KJ含有MF飼料を16週間摂取させた。その結果、KJ摂取がモリス水迷路試験で評価された空間記憶学習能力の低下を有意に抑制することが明らかとなった。また、各種酸化ストレスマーカーおよび抗酸化物質の濃度を指標とした酸化ストレス状態を有意に改善することが示された。認知機能低下抑制の分子メカニズムとして、脳における熱ショックタンパク質(HSP : Heat shock protein)70の高発現が示唆された。HSP70は、脳における異常タンパク質の凝集抑制により神経変性疾患の予防に寄与している分子シャペロンである。さらに、HSP70誘導の有効成分候補として、ポリフェノールの1種である1-sinapoyl-2-feruloylgentiobioseを同定した。

 第3章では、学習記憶に重要な脳の部位である海馬に焦点を当て、供試マウスの海馬での遺伝子発現変動を網羅的に解析することを目的とした。SAMP8を2群に群分けし、コントロール群にはAIN-93M飼料(通常食)を、KE群には0.05%(w/w)ケール抽出物(KE : Kale extract)含有AIN-93M飼料を31週間摂取させた。空間記憶学習能力をバーンズ迷路試験により評価したところ、KE摂取によるSAMP8の認知機能低下抑制が確認された。DNAマイクロアレイによる海馬遺伝子発現解析の結果、KE摂取はGタンパク質共役受容体に関連した経路の遺伝子を有意に高発現させることが示された。一方、補体・血液凝固系および焦点接着-PI3K-Akt-mTORの経路については、有意な発現抑制が認められた。高発現の経路には神経伝達物質の受容体に関する遺伝子が、低発現の経路には血栓形成などに関する遺伝子が含まれていた。したがって、これらの遺伝子発現変動がKE摂取による認知機能低下抑制に関与していることが推察された。

 第4章では、総括および今後の展望について述べている。本研究により、ケールの長期摂取が加齢に伴う認知機能低下の抑制や認知症の予防に有効であることが示された。また、その分子メカニズムの一端として、全脳におけるHSP70誘導や、海馬における神経伝達物質受容体の活性化などの関与が明らかとなった。本研究の知見が、安全かつ有効なアンチェイジング食品の開発に活用され、人々のQOL向上に広く貢献できることを期待する。

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