Department of Infectious Diseases, Shaanxi Provincial People's Hospital and The Affiliated Hospital of Xi'an Medical University, Xi'an, Shaanxi 710068, P.R. China.
The Third Department of Neurology, Shaanxi Provincial People's Hospital and The Affiliated Hospital of Xi'an Medical University, Xi'an, Shaanxi 710068, P.R. China.
Mol Med Rep. 2021 Apr;23(4). doi: 10.3892/mmr.2021.11913. Epub 2021 Feb 12.
During embryonic cortical development, radial glial cells (RGCs) are the major source of neurons, and these also serve as a supportive scaffold to guide neuronal migration. Similar to Vimentin, glial fibrillary acidic protein (GFAP) is one of the major intermediate filament proteins present in glial cells. Previous studies confirmed that prenatal ethanol exposure (PEE) significantly affected the levels of GFAP and increased the disassembly of radial glial fibers. GFAPδ is a variant of GFAP that is specifically expressed in RGCs; however, to the best of our knowledge, there are no reports regarding how PEE influences its expression during cortical development. In the present study, the effects of PEE on the expression and distribution of GFAPδ during early cortical development were assessed. It was found that PEE significantly decreased the expression levels of GFAP and GFAPδ. Using double immunostaining, GFAPδ was identified to be specifically expressed in apical and basal RGCs, and was co‑localized with other intermediate filament proteins, such as GFAP, Nestin and Vimentin. Additionally, PEE significantly affected the morphology of radial glial fibers and altered the behavior of RGCs. The loss of GFAPδ accelerated the transformation of RGCs into astrocytes. Using co‑immunostaining with Ki67 or phospho‑histone H3, GFAPδ+ cells were observed to be proliferative or mitotic cells, and ethanol treatment significantly decreased the proliferative or mitotic activities of GFAPδ+ RGCs. Taken together, the results suggested that PEE altered the expression patterns of GFAPδ and impaired the development of radial glial fibers and RGC behavior. The results of the present study provided evidence that GFAPδ may be a promising target to rescue the damage induced by PEE.
在胚胎皮质发育过程中，放射状胶质细胞（RGCs）是神经元的主要来源，它们也作为支持支架来指导神经元迁移。与波形蛋白一样，神经胶质纤维酸性蛋白（GFAP）是胶质细胞中存在的主要中间丝蛋白之一。先前的研究证实，产前乙醇暴露（PEE）显著影响 GFAP 的水平，并增加放射状胶质纤维的解体。GFAPδ 是 GFAP 的一种变体，特异性表达于 RGCs；然而，据我们所知，目前尚无关于 PEE 如何影响其在皮质发育过程中表达的报道。在本研究中，评估了 PEE 对早期皮质发育过程中 GFAPδ 表达和分布的影响。结果发现，PEE 显著降低了 GFAP 和 GFAPδ 的表达水平。通过双重免疫染色，鉴定出 GFAPδ 特异性表达于顶端和基底 RGCs，并与其他中间丝蛋白（如 GFAP、Nestin 和 Vimentin）共定位。此外，PEE 显著影响放射状胶质纤维的形态，并改变 RGCs 的行为。GFAPδ 的缺失加速了 RGC 向星形胶质细胞的转化。通过与 Ki67 或磷酸化组蛋白 H3 的共免疫染色，观察到 GFAPδ+细胞是增殖或有丝分裂细胞，乙醇处理显著降低了 GFAPδ+RGCs 的增殖或有丝分裂活性。综上所述，这些结果表明 PEE 改变了 GFAPδ 的表达模式，并损害了放射状胶质纤维和 RGC 行为的发育。本研究的结果提供了证据表明，GFAPδ 可能是拯救 PEE 诱导损伤的有希望的靶点。
