Role of complement regulatory factors in synapse pruning and in schizophrenia pathogeny

• Project/Area Number: 24591687
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Psychiatric science
• Research Institution: Nara Medical University
• Principal Investigator: KISHIMOTO Toshifumi 奈良県立医科大学, 医学部, 教授 (60201456)
• Co-Investigator(Kenkyū-buntansha): TSUBOI Akio 奈良県立医科大学, 医学部, 教授 (20163868) ; FUKAMI Shin-ichi 奈良県立医科大学, 医学部, 助教 (90424150)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000); Fiscal Year 2014: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2013: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2012: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: 統合失調症 / シナプス / 補体 / iPS細胞

Outline of Final Research Achievements

The pathology or pathophysiology of schizophrenia is still unclear. Recent genetic studies revealed complement regulatory factors as schizophrenia candidate genes. Additionally, studies of cell biology and neuroimmunology have reported activation of complement cascade plays an important role in synapse pruning in developing mouse brain. According to these findings, we suppose the deficit of synapse pruning due to complement dysregulation as a new pathological model of schizophrenia. In our study of cell culture model, neurons differentiated from iPSCs of schizophrenia patient and his discordant twin sibling showed lower expression of complement regulatory factor CSMD1 than that of control subject, and synapse formation was impaired in neurons of schizophrenia patient.