Contributions of Toll-like receptor-mediated regulations of proliferation and differentiation of subventricular zone neural stem cells on sulcogyrogenesis

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K06741
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 48010:Anatomy-related
• Research Institution: Tsukuba International University
• Principal Investigator: Sawada Kazuhiko つくば国際大学, 医療保健学部, 教授(移行) (10284324)
• Co-Investigator(Kenkyū-buntansha): 小林 哲也 埼玉大学, 理工学研究科, 教授 (00195794)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: 大脳皮質 / 脳溝 / 脳回 / 神経発生 / リポポリサッカリド / MRI

Outline of Final Research Achievements

Ferret pups were given a subcutaneous injection of lipopolysaccharide (LPS) at 500 μg/g of body weight) on postnatal days (PDs) 6 and 7. Furthermore, EdU and BrdU were administered on PDs 5 and 7, respectively, to label the post-proliferative and proliferating cells in the subventricular zone (SVZ) of the developing cerebral cortex. LPS exposure facilitated the proliferation of SVZ progenitors, which consisted of the basal radial glia and intermediate progenitors (IPs), and the differentiation of IPs into immature cortical neurons on PD 7. T1-weight MR images were acquired from the fixed brains of LPS-exposed ferrets. LPS exposure decreased the degree of cortical infolging in the frontal and parietal cortical regions. The findings revealed that neonatal LPS exposure alters the sulcogyrogenesis in the cortex. This may be an outcome of LPS-mediated the differentiative division of intermediate progenitors during the cerebral corticohistogenesis.

Free Research Field

解剖学

Academic Significance and Societal Importance of the Research Achievements

リポポリサッカリド(LPS)はグラム陰性菌の内毒素で、動物を用いた胎生期／新生仔期の曝露実験は、仔動物の自閉スペクトラム症(ASD)様行動異常を引き起こす。本研究では、新生仔期のLPS曝露が大脳皮質の発生においてintermediate progenitors(神経前駆細胞)からの皮質ニューロンの産生を促し、脳溝形成に影響を及ぼすことが明らかにした。この結果は、ASD様行動異常に関連した大脳皮質の形態異常がLPSによる皮質ニューロンの発生異常に起因することを示唆し、細菌感染による自然免疫の賦活化が脳発達障害を引き起こす可能性を示すものである。