Study on mechanism underlying schizophrenia development by carbonyl stress
Project/Area Number |
18K06977
|
Research Category |
Grant-in-Aid for Scientific Research (C)
|
Allocation Type | Multi-year Fund |
Section | 一般 |
Review Section |
Basic Section 49010:Pathological biochemistry-related
|
Research Institution | Tokyo Metropolitan Institute of Medical Science |
Principal Investigator |
TORIUMI Kazuya 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, 主任研究員 (10549421)
|
Project Period (FY) |
2018-04-01 – 2022-03-31
|
Project Status |
Completed (Fiscal Year 2021)
|
Budget Amount *help |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2019: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
Fiscal Year 2018: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
|
Keywords | カルボニルストレス / 統合失調症 / メチルグリオキサール / GLO1 / ビタミンB6 / ミトコンドリア / 酸化ストレス / 前頭皮質 / Glo1 / WGCNA / ペントシジン |
Outline of Final Research Achievements |
Methylglyoxal (MG) is a highly reactive and toxic molecule. We have previously reported that a subgroup of patients with schizophrenia showed dysfunction of GLO1, an enzyme to detoxify MG, and low levels of vitamin B6 (VB6), which works as a scavenger against MG. In this study, we generated a novel mouse model that reflects the pathological condition by feeding Glo1 knockout (KO) mice with a VB6-deficient diet, and evaluated the effects of the impaired MG detoxification mechanism on brain function. As a result, the mice showed MG accumulation in the brain and exhibited schizophrenia-like behavioral deficits. In addition, the mice exhibited abnormal expression of genes related to mitochondrial function in the prefrontal cortex, leading to dysfunction of mitochondrial respiratory chain and enhanced oxidative stress.
|
Academic Significance and Societal Importance of the Research Achievements |
今回明らかになった結果は、MG除去機構の障害であるGLO1機能障害とVB6欠損が組み合わさることで、脳内においてMGが蓄積し、前頭皮質におけるミトコンドリアの機能障害及び酸化ストレスの亢進が生じ、結果として統合失調症様行動障害が引き起こされていることを示唆するものである。 本研究成果は、MG除去機構の障害が統合失調症の発症に関与していることを示した初めての研究成果である。本研究で明らかになった障害メカニズムを考慮すると、MG除去機構障害(GLO1機能障害とVB6欠損)を有する患者さんに対しては、酸化ストレスを防ぐ抗酸化物質やVB6の補充が新たな治療戦略として有効である可能性がある。
|
Report
(5 results)
Research Products
(62 results)
-
-
-
-
-
[Journal Article] Advanced glycation end products and cognitive impairment in schizophrenia2021
Author(s)
Kobori Akiko、Miyashita Mitsuhiro、Miyano Yasuhiro、Suzuki Kazuhiro、Toriumi Kazuya、Niizato Kazuhiro、Oshima Kenichi、Imai Atsushi、Nagase Yukihiro、Yoshikawa Akane、Horiuchi Yasue、Yamasaki Syudo、Nishida Atsushi、Usami Satoshi、Takizawa Shunya、Itokawa Masanari、Arai Heii、Arai Makoto
-
Journal Title
PLOS ONE
Volume: 16
Issue: 5
Pages: e0251283-e0251283
DOI
Related Report
Peer Reviewed / Open Access
-
-
-
-
-
-
-
[Journal Article] Cooperation of LIM domain-binding 2 (LDB2) with EGR in the pathogenesis of schizophrenia.2021
Author(s)
Ohnishi T, Kiyama Y, Arima-Yoshida F, Kadota M, Ichikawa T, Yamada K, Watanabe A, Ohba H, Tanaka K, Nakaya A, Horiuchi Y, Iwayama Y, Toyoshima M, Ogawa I, Shimamoto-Mitsuyama C, Maekawa M, Balan S, Arai M, Miyashita M, Toriumi K, et al.
-
Journal Title
EMBO Mol Med
Volume: 13
Issue: 4
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
-
[Journal Article] Evolution of DNA Methylation in the Human Brain.2021
Author(s)
Jeong H, Mendizabal I, Berto S, Chatterjee P, Layman T, Usui N, Toriumi K, Douglas C, Singh D, Huh I, Preuss T, Konopka G, Soojin VYI.
-
Journal Title
Nat Commun
Volume: 12
Issue: 1
Pages: 2021-2021
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
-
-
[Journal Article] Accelerated evolution of oligodendrocytes in the human brain2019
Author(s)
Berto Stefano*、Mendizabal Isabel*、Usui Noriyoshi*、Toriumi Kazuya*、Chatterjee Paramita、Douglas Connor、Tamminga Carol A.、Preuss Todd M.、Yi Soojin V.、Konopka Genevieve [*Co-first authors]
-
Journal Title
Proceedings of the National Academy of Sciences
Volume: 116
Issue: 48
Pages: 24334-24342
DOI
Related Report
Peer Reviewed / Int'l Joint Research
-
-
-
[Journal Article] Pyridoxamine, A Novel Treatment For Schizophrenia With Enhanced Carbonyl Stress.2018
Author(s)
Itokawa M, Miyashita M, Arai M, Dan T, Takahashi K, Tokunaga T, Ishimoto K, Toriumi K, Ichikawa T, Horiuchi Y, Kobori A, Usami S, Yoshikawa T, Amano N, Washizuka S, Okazaki Y, Miyata T.
-
Journal Title
Psychiatry Clin Neurosci.
Volume: 72(1)
Issue: 1
Pages: 35-44
DOI
Related Report
Peer Reviewed / Open Access
-
[Journal Article] Protein kinase C δ gene depletion protects against methamphetamine-induced impairments in recognition memory and ERK1/2 signaling via up-regulation of glutathione peroxidase-1 gene.2018
Author(s)
Tran TV, Shin EJ, Nguyen LTL, Lee Y, Kim DJ, Jeong JH, Jang CG, Nah SY, Toriumi K, Nabeshima T, Yamada K, Kim HC.
-
Journal Title
Mol Neurobiol
Volume: 印刷中
Pages: 4136-4159
DOI
Related Report
Peer Reviewed / Int'l Joint Research
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
[Presentation] カルボニルストレス性統合失調症患者由来 iPS細胞の解析2019
Author(s)
堀内泰江, 石川充, 小幡菜々子, 畠中真依, 許絲茵, 小池伸, 鳥海和也、宮下光弘 宮岡祐一郎, 小笠原裕樹, 勝田奈那, 永井竜児, 岡野栄之, 糸川昌成, 新井誠.
Organizer
第29回日本メイラード学会
Related Report
-
-
-
-
[Presentation] Effect of vitamin B6-deficiency on mouse behavior and monoaminergic system2018
Author(s)
Kazuya Toriumi, Mitsuhiro Miyashita, Yasue Horiuchi, Kazuhiro Suzuki, Akiko Kobori, Izumi Nohara, Yukiko Shimada, Emiko Hama, Nanako Obata, Masanari Itokawa, Makoto Arai
Organizer
13th International Symposium on the Maillard Reaction
Related Report
Int'l Joint Research
-
-
-
-
-