Exploration and Identification of schizophrenia related lipid molecules

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K21622
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Neurochemistry/Neuropharmacology; Psychiatric science
• Research Institution: Institute of Physical and Chemical Research
• Principal Investigator: Shimamoto Chie 国立研究開発法人理化学研究所, 脳神経科学研究センター, 基礎科学特別研究員 (90755117)
• Research Collaborator: Ohnishi Tetsuo ; Maekawa Motoko ; Iwayama Yoshimi ; Balan Shabeesh ; Esaki Kayoko ; Watanabe Akiko ; Ohba Hisako ; Toyota Tomoko ; Dean Brian ; Yoshikawa Takeo
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: 統合失調症 / 死後脳 / 脂質

Outline of Final Research Achievements

In this study, we hypothesized that abnormal lipid homeostasis is involved in the pathology of schizophrenia.
First, we analyzed the mouse model (Fabp7 KO mouse) using imaging mass spectrometry. We found that they showed tended to have an altered abundance in some kinds of phospholipids in the schizophrenia-related brain regions. Next, we performed lipid analysis using liquid chromatography and gene expression analyses using the postmortem corpus callosum from schizophrenics and unaffected controls. We identified lipid combinations associated with schizophrenia and found that low expression levels of lipid metabolism-related genes and their potential upstream transcription factors in schizophrenia.
Our findings suggest the possibility that abnormal lipid synthesis/remodeling may be molecular underpinnings for the corpus callosum abnormalities reported in schizophrenia.

Free Research Field

分子生物学

Academic Significance and Societal Importance of the Research Achievements

代表的な精神疾患の一つである統合失調症は現存の治療法で完治が困難であることから、新規予防・診断・治療法の開発が強く求められている。近年、統合失調症の病態生理と脂質（特に脂肪酸）との関連性が注目されているが、その具体的なメカニズムについては不明なままである。そこで本研究では、1）モデルマウスの脳の脂質解析、2）ヒト死後脳の脂質定量解析及び遺伝子発現解析を行い、統合失調症の病態と脂質との関係解明を目指した。解析の結果、一部の統合失調症患者の脳梁でみられる病態に特定の脂質生合成代謝異常が関与している可能性が高まった。