Pathophysiological analysis of schizophrenia and ASD by using the co-culture system of macrophages and hiPSC-derived neurons.

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K08025
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 52030:Psychiatry-related
• Research Institution: Nara Medical University
• Principal Investigator: Toritsuka Michihiro 奈良県立医科大学, 医学部, 講師 (20588529)
• Co-Investigator(Kenkyū-buntansha): 芳野 浩樹 奈良県立医科大学, 医学部, 研究員 (10347560)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: ヒトiPS細胞 / マクロファージ / ASD / 統合失調症

Outline of Final Research Achievements

To elucidate the pathology of schizophrenia and autism spectrum disorder, we tried to investigate the effect of immune cells on synapse formation of neurons, because the synaptic hypothesis has been proposed for the pathological hypothesis of both disorders. Peripheral macrophages, of which cytokine expression was correlated with the severity of ASD, were used as immune cells and co-cultured with human iPS cell-derived neurons. The results is that both M1/M2 macrophages of patients with ASD had a greater impact on neurons compared to typically developed control group. We would like to approach the elucidation of disease pathophysiology and to establish the drug screening system by investigating further molecular pathways.

Free Research Field

精神医学

Academic Significance and Societal Importance of the Research Achievements

マクロファージは貪食能を有するのみならず、サイトカインや栄養因子を分泌する機能を持ち、マイクログリアと同様に神経細胞・グリア細胞の増殖・生存やシナプス形成に関わることがわかってきている。患者生体脳からマイクログリアを得ることはほぼ不可能であるため、簡便に採取可能な末梢マクロファージを中心に解析しバイオマーカーとなりうる指標を見出すことで、安価に多数のサンプルを解析し病態解明と創薬の可能性に踏み込める点に本研究の意義がある。実際にASD群での違いが見いだせたことは有意義である。