PDF(Pubmed)
Abstract：
Neuronal CX3CL1 suppressed microglial inflammation by binding to its receptor CX3CR1 expressed on microglia. Neuronal autophagy was prominently activated by cerebral ischemia, whereas CX3CL1 expression in autophagic neurons was conversely down-regulated to exacerbate microglial inflammation. Accordingly, this study was meant to investigate whether ischemia-activated microglial inflammation could be repressed by promoting CX3CL1 expression via the attenuation of neuronal autophagy. Immunofluorescence showed that autophagy predominantly occurred in neurons but barely in microglia. Western blot and immunofluorescence demonstrated that attenuating HT22 autophagy significantly increased its CX3CL1 expression and subsequently mitigated the BV2-mediated inflammatory responses, as indicated by decreased inflammatory factors of NF-κB-p65, IL-6, IL-1β, TNF-α, and PGE2. Meanwhile, CCK-8, Nissl staining, and FJC staining showed that an OGD (Oxygen-glycogen deprivation)-created neuronal injury was greatly alleviated by CX3CL1-suppressed microglial inflammation. Contrarily, elevating HT22 autophagy markedly decreased its CX3CL1 expression, which consequently worsened microglial inflammation and the neuronal injury. Our data suggests that attenuating neuronal autophagy may be an effective method to alleviate a microglial inflammatory injury after an ischemic stroke.
摘要：
神经元CX3CL1通过与小胶质细胞上表达的受体CX3CR1结合抑制小胶质细胞炎症。脑缺血显著激活神经元自噬，而自噬神经元中CX3CL1的表达则相反下调,加剧了小胶质细胞炎症.因此，这项研究旨在研究缺血激活的小胶质细胞炎症是否可以通过减弱神经元自噬促进CX3CL1表达来抑制.免疫荧光显示自噬主要发生在神经元中，但很少发生在小胶质细胞中。蛋白质印迹和免疫荧光表明，减弱HT22自噬显著增加其CX3CL1表达，随后减轻BV2介导的炎症反应，炎症因子NF-κB-p65、IL-6、IL-1β水平降低,TNF-α,和PGE2。同时,CCK-8,Nissl染色,和FJC染色显示，CX3CL1抑制的小胶质细胞炎症极大地减轻了OGD（氧糖原剥夺）产生的神经元损伤。相反，升高HT22自噬显著降低其CX3CL1表达，从而恶化小胶质细胞炎症和神经元损伤。我们的数据表明，减弱神经元自噬可能是减轻缺血性卒中后小胶质细胞炎症损伤的有效方法。
