he Impact of Perinatal Stress on Neural Stem Cell Differentiation and Its Mechanisms

2023 Fiscal Year Final Research Report

• Project/Area Number: 18K07891
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 52050:Embryonic medicine and pediatrics-related
• Research Institution: Showa University (2019, 2023); Kwansei Gakuin University (2018)
• Principal Investigator: Adachi Naoki 昭和大学, 医学部, 准教授 (00450601)
• Co-Investigator(Kenkyū-buntansha): 鈴木 辰吾 香川大学, 医学部, 准教授 (50451430)
• Project Period (FY): 2018-04-01 – 2022-03-31
• Keywords: グルココルチコイド / 神経幹細胞 / 分化

Outline of Final Research Achievements

This study thoroughly analyzed the impact of glucocorticoids on the differentiation of neural stem cells. In vitro experiments demonstrated that glucocorticoids promote differentiation into astrocytes while inhibiting differentiation into oligodendrocytes. Two intracellular signaling pathways involved in this disruption of differentiation balance were identified. Additionally, next-generation sequencing technology was used to identify the gene groups associated with these processes.

Although in vivo experiments did not progress as initially planned, we established a system for tracking the differentiation fate of neural stem cells using CRISPR-Cas9 genome editing technology. This advancement will enable future analysis of how fetal exposure to glucocorticoids affects brain function later in life.

Free Research Field

神経科学

Academic Significance and Societal Importance of the Research Achievements

本研究の成果は、グルココルチコイドが神経幹細胞の分化運命に与える影響を分子レベルで解明し、周産期のストレスが長期的な脳機能に与える影響を示したことである。この知見は、精神疾患の予防や治療法の開発に寄与するだけでなく、周産期のストレス管理やステロイド使用のガイドライン策定にも大きく貢献する。
また、グルココルチコイドによる神経幹細胞の運命決定攪乱に関わる細胞内シグナルに関する知見は、今後、胎内ストレスが脳の発達に与える悪影響を緩和するための特定のシグナル経路を標的とした新たな治療戦略の開発に繋がる可能性がある。