Molecular mechanisms of glycative stress exposure in patients with schizophrenia

2018 Fiscal Year Final Research Report

• Project/Area Number: 16H05380
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Psychiatric science
• Research Institution: Tokyo Metropolitan Institute of Medical Science
• Principal Investigator: ARAI Makoto 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, プロジェクトリーダー (80356253)
• Co-Investigator(Kenkyū-buntansha): 瀧澤 俊也 東海大学, 医学部, 教授 (70197234)
• Research Collaborator: HORIUCHI Yasue ; MIYASHITA Kazuhiro ; TORIUMI Kazuya ; SUZUKI Kazuhiro ; YOSHIKAWA Akane
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: 糖化 / 統合失調症 / GLO1 / カルボニルストレス / グリケーション / ライフコース

Outline of Final Research Achievements

Glycation is the abnormal accumulation of dicarbonyl metabolites leading to increased modification of protein. Glycative stress is a risk factor of various diseases in the life stages, such as diabetes, heart disease, dementia and psychiatric disorders. However, the developmental effects and health-related impacts of glycative stress in the life stages and the molecular basis of these effects are unknown. We found several schizophrenic patients with novel heterozygous frameshift and missense mutations in GLO1 gene with 40-50% and 15-20% reduction of enzymatic activity, respectively. GLO1 is one of enzymes to detoxify reactive carbonyl compounds such as methylglyoxal, preventing the eventual formation of AGEs. In order to evaluate effects of GLO1 deficits on behavior, we generated Glo1 knockout mice and assessed their behavioral phenotypes.

Free Research Field

分子精神医学、分子神経科学、生物学的精神医学

Academic Significance and Societal Importance of the Research Achievements

精神疾患の多くの症例において糖尿病、心血管疾患、肥満など様々な合併症が問題視されている。身体疾患の増悪とも関連のあるカルボニルストレスを軸としてデータ資源を十分に有効活用することは、早期からの精神疾患・身体疾患の予防介入、健康増進に資する予防医学に貢献できるものと考えられ、その社会的意義は高い。統合失調症をはじめとする精神疾患の発症や病態の分子メカニズムを糖化ストレスの観点から理解する事は学術的に意義が高い。