Premature Neural Progenitor Cell Differentiation Into Astrocytes in Retinoic Acid-Induced Spina Bifida Rat Model.
Premature Neural Progenitor Cell Differentiation Into Astrocytes in Retinoic Acid-Induced Spina Bifida Rat Model.
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DOI：
10.3389/fnmol.2022.888351
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发表时间：
2022
影响因子：
4.8
通讯作者：
Peiro, Jose L.
中科院分区：
文献类型：
--
作者：
Oria, Marc;Pathak, Bedika;Li, Zhen;Bakri, Kenan;Gouwens, Kara;Varela, Maria Florencia;Lampe, Kristin;Murphy, Kendall P.;Lin, Chia-Ying;Peiro, Jose L.
关键词：
在胚胎脊髓发育期间，神经祖细胞（NPC）在脊髓内的精确时间和位置产生三种主要细胞系：神经元、少突胶质细胞和星形胶质细胞。最近的研究表明，在脊柱裂的动物模型中，早期星形细胞发生可能在与这种情况相关的神经元功能障碍中发挥作用。然而，到目前为止，脊柱裂的这种早期星形胶质细胞反应的病理生理机制知之甚少。本研究旨在使用维甲酸诱导的脊柱裂大鼠模型表征Pax 6+、Olig 2+或Nkx2.2+ NPC随时间的早期星形胶质细胞增生的发展。在三个胎龄（E15、E17和E20），分析了维甲酸诱导脊柱裂胎仔、其健康同胞对照或溶剂对照处理胎仔的脊髓。结果表明，与对照组相比，过早的星形胶质细胞增生和星形胶质细胞活化与病变中Pax 6+、Olig 2+和Nkx2.2+ NPC的存在改变相关。最后，这种反应与Notch-BMP信号通路相关基因的升高有关。两者合计，NPC图案化因子表达的变化与Notch-BMP信号的上调可能是负责在维甲酸诱导的脊柱裂模型中观察到的脊髓中的星形细胞发生模式的改变。
During embryonic spinal cord development, neural progenitor cells (NPCs) generate three major cell lines: neurons, oligodendrocytes, and astrocytes at precise times and locations within the spinal cord. Recent studies demonstrate early astrogenesis in animal models of spina bifida, which may play a role in neuronal dysfunction associated with this condition. However, to date, the pathophysiological mechanisms related to this early astrocytic response in spina bifida are poorly understood. This study aimed to characterize the development of early astrogliosis over time from Pax6+, Olig2+, or Nkx2.2+ NPCs using a retinoic acid-induced spina bifida rat model. At three gestational ages (E15, E17, and E20), spinal cords from fetuses with retinoic acid-induced spina bifida, their healthy sibling controls, or fetuses treated with the vehicle control were analyzed. Results indicated that premature astrogliosis and astrocytic activation were associated with an altered presence of Pax6+, Olig2+, and Nkx2.2+ NPCs in the lesion compared to the controls. Finally, this response correlated with an elevation in genes involved in the Notch-BMP signaling pathway. Taken together, changes in NPC patterning factor expression with Notch-BMP signaling upregulation may be responsible for the altered astrogenesis patterns observed in the spinal cord in a retinoic acid-induced spina bifida model.
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