Elucidation of pathologic mechanism using iPS cells derived from schizophrenia patients

2016 Fiscal Year Final Research Report

• Project Area: Unraveling micro-endophenotypes of psychiatric disorders at the molecular, cellular and circuit levels.
• Project/Area Number: 24116002
• Research Category: Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area)
• Allocation Type: Single-year Grants
• Review Section: Biological Sciences
• Research Institution: Institute of Physical and Chemical Research
• Principal Investigator: YOSHIKAWA TAKEO 国立研究開発法人理化学研究所, 脳科学総合研究センター, チームリーダー (30249958)
• Co-Investigator(Kenkyū-buntansha): 豊田 倫子 国立研究開発法人理化学研究所, 脳科学総合研究センター, 客員研究員 (20392045) ; 前川 素子 国立研究開発法人理化学研究所, 脳科学総合研究センター, 研究員 (50435731) ; 大西 哲生 国立研究開発法人理化学研究所, 脳科学総合研究センター, 副チームリーダー (80373281) ; 豊島 学 国立研究開発法人理化学研究所, 脳科学総合研究センター, 研究員 (90582750)
• Co-Investigator(Renkei-kenkyūsha): KOBAYASHI Toshihide 国立研究開発法人理化学研究所, 佐甲細胞情報研究室, 客員主管研究員 (60162004)
• Project Period (FY): 2012-06-28 – 2017-03-31
• Keywords: 統合失調症 / 22q11.2欠失 / iPS細胞 / カルボニルストレス / 神経発達 / 終末糖化産物 / miRNA / コピー数多型

Outline of Final Research Achievements

We studied iPS cells derived from schizophrenia with the microdeletion of chromosome 22q11.2 and with impaired GLO1 gene whose protein product is involved in the scavenging of carbonyl stress. In these studies, we focused on the schizophrenia theory of “abnormal neurodevelopment”.We observed disturbed differentiation efficiencies in patients’iPS cell-derived neurospheres and neurons. Those defects of neural differentiations were partially rescued by an inhibitor of p38 (for 22q11.2 deletion) or by scavengers of carbonyl stress (for GLO1 mutation), suggesting an importance of rectifying abnormal neural differentiations in early neurodevelopmental stage.
We could also confirm that abnormal neural differentiations are seen in patients’ postmortem brains, by examining the expression ratio of neuronal and glial markers.

Free Research Field

精神医学、精神科遺伝学、分子細胞生物学