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首页> 外文期刊>The European Journal of Neuroscience >Dynamic cell type-specific expression of Nrf2 after traumatic brain injury in mice
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Dynamic cell type-specific expression of Nrf2 after traumatic brain injury in mice

机译:小鼠创伤性脑损伤后NRF2的动态细胞类型特异性表达

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摘要

Nrf2 plays a pivotal role in antioxidant response and anti-inflammation after traumatic brain injury (TBI), and its deletion aggravates TBI-induced brain damage. Previous studies have demonstrated that Nrf2 is activated post TBI, but dynamic changes in expression and cell type-specific characteristics remain unclear. In this study, the Feeney weight-drop contusion model was conducted to mimic TBI, and the ipsilateral cerebral cortex was collected at 1, 3, 7 and 14 days post TBI (dpi). Nrf2 protein levels were observed by western blot. Cell type-specific localization of Nrf2 after TBI was detected at different time intervals by double immunofluorescence staining. NeuN, GFAP, IBA1 and NG2 were used as cell type-specific markers to neurons, astrocytes, microglia and NG2 glia, respectively. After TBI, Nrf2 protein levels peaked at 1 dpi. Robust transient Nrf2 accumulation was co-localized with neurons, which was predominant at 1 dpi. Continuous weak Nrf2 expression was detected in activated astrocytes, and the number of double positive cells peaked at 7 dpi. Inducible widespread immunostaining of Nrf2 was observed in the nucleus of the microglia, and the number of Nrf2+ microglia peaked at 7 dpi. In addition, we also explored colocalization of Nrf2 in NG2 glia, in which the percentage of Nrf2+ in NG2 glia reached a climax at 3 dpi. This study reveals that the accumulation of endogenous Nrf2 might mediate different pathophysical roles in neurons and glias after TBI, the cell-type specific and time-dependent expression provide insights to explain the roles of Nrf2 in different neural cells.
机译:NRF2在创伤性脑损伤(TBI)后在抗氧化反应和抗炎中发挥枢轴作用,其缺失会加剧TBI诱导的脑损伤。以前的研究表明,NRF2被激活后TBI后,但表达和细胞类型特征的动态变化仍不清楚。在这项研究中,Feeney屈服挫伤模型进行了模拟TBI,并且在TBI(DPI)后1,3,7和14天收集同侧脑皮质。通过Western印迹观察NRF2蛋白质水平。通过双免疫荧光染色以不同的时间间隔检测TBI后NRF2的细胞类型特异性。 NeUN,GFAP,IBA1和NG2分别用作细胞类型特异性标记,分别与神经元,星形胶质细胞,小胶质细胞和NG2胶质细胞。 TBI后,NRF2蛋白水平在1 dpi下达到峰值。强大的瞬时NRF2积累与神经元共同定位,其在1 dpi处是主要的。在活性的星形胶质细胞中检测到连续弱NRF2表达,并且在7 dpi上达到双阳性细胞的数量。在微胶质细胞核的核中观察到NRF2的诱导型广泛免疫染色,NRF2 +微胶质细胞的数量在7dpi下达到峰值。此外,我们还探讨了NG2 Glia中NRF2的分致化,其中NG2 Glia中NRF2 +的百分比在3 dpi达到了高潮。该研究表明,在TBI之后,内源性NRF2的积累可能在神经元和眩光中介导不同的病理物理作用,细胞型特异性和时间依赖性表达提供了解释NRF2在不同神经细胞中的角色的见解。

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  • 作者单位

    China Med Univ Sch Forens Med Dept Forens Pathol Shenyang Liaoning Peoples R China;

    China Med Univ Sch Forens Med Dept Forens Pathol Shenyang Liaoning Peoples R China;

    China Med Univ Sch Forens Med Dept Forens Pathol Shenyang Liaoning Peoples R China;

    China Med Univ Coll Basic Med Sci Dept Histol &

    Embryol Shenyang Liaoning Peoples R China;

    China Med Univ Sch Forens Med Dept Forens Pathol Shenyang Liaoning Peoples R China;

    China Med Univ Sch Forens Med Dept Forens Pathol Shenyang Liaoning Peoples R China;

    China Med Univ Sch Forens Med Dept Forens Pathol Shenyang Liaoning Peoples R China;

    China Med Univ Sch Forens Med Dept Forens Pathol Shenyang Liaoning Peoples R China;

    China Med Univ Sch Forens Med Dept Forens Pathol Shenyang Liaoning Peoples R China;

    China Med Univ Sch Forens Med Dept Forens Pathol Shenyang Liaoning Peoples R China;

    China Med Univ Sch Forens Med Dept Forens Pathol Shenyang Liaoning Peoples R China;

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  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 神经病学与精神病学;
  • 关键词

    astrocytes; microglia; neurons; NG2 glia; nuclear factor erythroid 2-related factor 2; traumatic brain injury;

    机译:星形胶质细胞;微胶质细胞;神经元;NG2 Glia;核因子红外2相关因子2;创伤性脑损伤;

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