Elucidating the role of immune system actors in brain development

2023 Fiscal Year Final Research Report

• Project/Area Number: 22K19365
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Review Section: Medium-sized Section 46:Neuroscience and related fields
• Research Institution: Keio University
• Principal Investigator: Nakajima Kazunori 慶應義塾大学, 医学部(信濃町), 教授 (90280734)
• Project Period (FY): 2022-06-30 – 2024-03-31
• Keywords: 母由来免疫グロブリン / 抑制性ニューロン / 大脳皮質発生

Outline of Final Research Achievements

Maternal immunoglobulins (Ig) flow into the offspring across the placenta. However, there is a risk of influx of brain-injurious Ig into the developing brain, because the blood-brain barrier is still immature. This may suggest some unknown surpassing significance of the mother-derived Ig during brain development. In this study, we first showed that almost all of the Ig detected in the embryonic brain is mother-derived IgG. Next, we identified cells in the embryonic brain that receive mother-derived IgG. Furthermore, we found that loss of mother-derived IgG, especially during the embryonic period, leads to an abnormal decrease in cortical inhibitory neurons after birth.

Free Research Field

発生神経生物学

Academic Significance and Societal Importance of the Research Achievements

胎生期の脳に母由来の免疫グロブリン（抗体分子Ig）が存在していることは古くから知られており、感染予防のためと考えられている。しかしながら、通常の胎生期脳には明らかな感染や炎症はなく、何らかの未知の機能が母由来Igにはあるのではないかと考えた。本研究では、母由来Igが生後の大脳皮質抑制性ニューロンの生存維持に重要な役割を有することを見出したが、抑制性ニューロンの異常は様々な精神神経疾患の病態と関係することが注目されており、臨床的にも意義のある成果と考えられる。