Elucidation of the mechanism of depression development focusing on protein misfolding.

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K06531
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 43020:Structural biochemistry-related
• Research Institution: Okayama University of Science
• Principal Investigator: Hashikawa Naoya 岡山理科大学, 理学部, 准教授 (60434982)
• Co-Investigator(Kenkyū-buntansha): 桜井 博 金沢大学, 保健学系, 教授 (00225848)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: うつ病 / 社会敗北ストレス / マウス / うつ様行動 / 熱ショックタンパク質 / アミロイド

Outline of Final Research Achievements

To clarify that depression is caused by protein misfolding, mice were exposed to 4 weeks of social defeat stress to search for proteins that aggregate in the brain hippocampus. The results showed that amyloid-β increased in the hippocampus of stressed mice. Induction of heat shock protein expression, which is involved in protein folding, in mice subjected to social defeat stress suppressed amyloid-β levels and depression-like behavior.
The results of this study revealed the possibility of increased amyloid-β as one of the causes of depressive-like behavior, and suggested that normalization of protein folding can suppress depressive-like behavior.

Free Research Field

精神神経科学

Academic Significance and Societal Importance of the Research Achievements

うつ病発症の原因となる新たなタンパク質の探索を行なった。その結果、ストレスを与えたマウスにおいてアミロイドβが増加し、アミロイドβの増加を抑制することでマウスのうつ様行動が減少することを明らかにした。今回の研究結果は、うつ病発症の原因の一つとしてアミロイドβ増加の可能性があることを明らかにし、今後のさらなる研究によりアミロイドβをターゲットとした新たなうつ病治療薬の開発が期待される。