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Assessment of radial glia in the frontal lobe of fetuses with Down syndrome.
Acta Neuropathologica Communications ( IF 6.2 ) Pub Date : 2020-08-20 , DOI: 10.1186/s40478-020-01015-3
Ana A Baburamani 1 , Regina T Vontell 1, 2 , Alena Uus 3 , Maximilian Pietsch 1, 3 , Prachi A Patkee 1 , Jo Wyatt-Ashmead 4 , Evonne C Chin-Smith 1 , Veena G Supramaniam 1 , J Donald Tournier 1, 3 , Maria Deprez 1, 3 , Mary A Rutherford 1
Affiliation  

Down syndrome (DS) occurs with triplication of human chromosome 21 and is associated with deviations in cortical development evidenced by simplified gyral appearance and reduced cortical surface area. Radial glia are neuronal and glial progenitors that also create a scaffolding structure essential for migrating neurons to reach cortical targets and therefore play a critical role in cortical development. The aim of this study was to characterise radial glial expression pattern and morphology in the frontal lobe of the developing human fetal brain with DS and age-matched controls. Secondly, we investigated whether microstructural information from in vivo magnetic resonance imaging (MRI) could reflect histological findings from human brain tissue samples. Immunohistochemistry was performed on paraffin-embedded human post-mortem brain tissue from nine fetuses and neonates with DS (15–39 gestational weeks (GW)) and nine euploid age-matched brains (18–39 GW). Radial glia markers CRYAB, HOPX, SOX2, GFAP and Vimentin were assessed in the Ventricular Zone, Subventricular Zone and Intermediate Zone. In vivo diffusion MRI was used to assess microstructure in these regions in one DS (21 GW) and one control (22 GW) fetal brain. We found a significant reduction in radial glial progenitor SOX2 and subtle deviations in radial glia expression (GFAP and Vimentin) prior to 24 GW in DS. In vivo, fetal MRI demonstrates underlying radial projections consistent with immunohistopathology. Radial glial alterations may contribute to the subsequent simplified gyral patterns and decreased cortical volumes observed in the DS brain. Recent advances in fetal MRI acquisition and analysis could provide non-invasive imaging-based biomarkers of early developmental deviations.

中文翻译:


唐氏综合症胎儿额叶放射状胶质细胞的评估。



唐氏综合症 (DS) 因人类 21 号染色体三倍体而发生,并与皮质发育偏差相关,表现为脑回外观简化和皮质表面积减少。放射状胶质细胞是神经元和神经胶质祖细胞,它们还创建了神经元迁移到达皮质目标所必需的支架结构,因此在皮质发育中发挥着关键作用。本研究的目的是通过 DS 和年龄匹配的对照来表征发育中的人类胎儿大脑额叶中放射状胶质细胞的表达模式和形态。其次,我们研究了体内磁共振成像(MRI)的微观结构信息是否可以反映人脑组织样本的组织学发现。对来自 9 个 DS 胎儿和新生儿(15-39 孕周 (GW))和 9 个年龄匹配的整倍体大脑(18-39 GW)的石蜡包埋的人类死后脑组织进行免疫组织化学分析。在心室区、室下区和中间区评估放射状胶质细胞标记物 CRYAB、HOPX、SOX2、GFAP 和波形蛋白。使用体内扩散 MRI 来评估一名 DS(21 GW)和一名对照(22 GW)胎儿大脑中这些区域的微观结构。我们发现在 DS 24 GW 之前,放射状胶质祖细胞 SOX2 显着减少,放射状胶质细胞表达(GFAP 和 Vimentin)存在细微偏差。在体内,胎儿 MRI 显示了与免疫组织病理学一致的潜在径向投影。放射状胶质细胞的改变可能导致随后在 DS 大脑中观察到的简化的回旋模式和减少的皮质体积。胎儿 MRI 采集和分析的最新进展可以提供早期发育偏差的基于非侵入性成像的生物标志物。
更新日期:2020-08-20
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