Research Centre for Encephalopathies and Transmissible Emerging Diseases - Institute for Health Research Aragón (IIS), University of Zaragoza, C/Miguel Servet 155, 50013 Zaragoza, Spain.
Int J Mol Sci. 2020 Aug 12;21(16):5779. doi: 10.3390/ijms21165779.
A recently published report on chronic dexamethasone treatment for natural scrapie supported the hypothesis of the potential failure of astroglia in the advanced stage of disease. Herein, we aimed to extend the aforementioned study on the effect of this anti-inflammatory therapy to the initial phase of scrapie, with the aim of elucidating the natural neuroinflammatory process occurring in this neurodegenerative disorder. The administration of this glucocorticoid resulted in an outstanding reduction in vacuolation and aberrant protein deposition (nearly null), and an increase in glial activation. Furthermore, evident suppression of IL-1R and IL-6 and the exacerbation of IL-1α, IL-2R, IL-10R and IFNγR were also demonstrated. Consequently, the early stage of the disease is characterized by an intact neuroglial response similar to that of healthy individuals attempting to re-establish homeostasis. A complex network of neuroinflammatory markers is involved from the very early stages of this prion disease, which probably becomes impaired in the more advanced stages. The in vivo animal model used herein provides essential observations on the pathogenesis of natural scrapie, as well as the possibility of establishing neuroglia as potential target cells for anti-inflammatory therapy.
最近发表的一篇关于慢性地塞米松治疗天然朊病毒病的报告支持了星形胶质细胞在疾病晚期可能失效的假说。在此，我们旨在将上述关于这种抗炎治疗对朊病毒病初始阶段影响的研究扩展到该神经退行性疾病中发生的自然神经炎症过程。这种糖皮质激素的给药导致空泡形成和异常蛋白沉积（几乎为零）显著减少，以及神经胶质激活增加。此外，还明显抑制了 IL-1R 和 IL-6，同时加剧了 IL-1α、IL-2R、IL-10R 和 IFNγR。因此，疾病的早期阶段表现为类似于健康个体试图重新建立体内平衡的完整神经胶质反应。从这种朊病毒病的早期阶段开始，就涉及到一个复杂的神经炎症标志物网络，而在更晚期阶段，这个网络可能会受损。本文中使用的体内动物模型为天然朊病毒病的发病机制提供了重要观察，并为将神经胶质作为抗炎治疗的潜在靶细胞提供了可能性。
