Mechanism of neuromodulatory effects by collagen peptides

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K05927
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 38050:Food sciences-related
• Research Institution: Utsunomiya University
• Principal Investigator: Mizushige Takafumi 宇都宮大学, 農学部, 准教授 (70571008)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: コラーゲンペプチド / うつ様行動 / ストレス

Outline of Final Research Achievements

We have previously found that collagen hydrolysate exhibited antidepressant-like activity. We also found that prolyl hydroxyproline (PO), which has circulated in the blood after ingestion of collagen hydrolysate, have exhibited antidepressant-like activity. In this study, we have shown that PO promotes hippocampal neurogenesis in mice and primary hippocampal neural progenitor cells. Collagen hydrolysate has increased hippocampal dopamine levels. In addition, the antidepressant-like activity of collagen hydrolysate has been disappeared with the injection of D1 receptor antagonists. In social defeat stress and neuroinflammatory activation models, collagen hydrolysate was also effective in depressive behavior. In summary, we found a novel antidepressant peptide from collagen hydrolysate and elucidated a part of mechanism in its antidepressant-like activity.

Free Research Field

生物化学

Academic Significance and Societal Importance of the Research Achievements

本研究において、うつ様行動を減少させる新規コラーゲン由来ジペプチドとしてプロリルヒドロキシプロリンを見出した。食品レベルやペプチド創薬レベルで、脳機能向上素材としての応用が期待される。コラーゲンは、哺乳類の生体内で最も多いタンパク質であり食品廃棄物の中にも多いとされ、食品廃棄物の削減につながる可能性もある。当該ペプチドは脳に移行し、脳内で直接的にドーパミン神経系の活性化、海馬神経新生の促進、神経炎症の抑制を介して抗うつ作用を発揮すると考えられた。本研究により、コラーゲン分解物の活性成分の同定とそのメカニズムの一端が明らかとなり、食品－神経相互作用の生理的意義解明につながる重要な知見を得た。