Up-regulated fractalkine (FKN) and its receptor CX3CR1 are involved in fructose-induced neuroinflammation: Suppression by curcumin
Up-regulated fractalkine (FKN) and its receptor CX3CR1 are involved in fructose-induced neuroinflammation: Suppression by curcumin
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上调的 fractalkine (FKN) 及其受体 CX3CR1 参与果糖诱导的神经炎症：姜黄素的抑制。
DOI：
10.1016/j.bbi.2016.01.001
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发表时间：
2016-11-01
影响因子：
15.1
通讯作者：
Kong, Ling-Dong
中科院分区：
文献类型：
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作者：
Xu, Min-Xuan;Yu, Rong;Kong, Ling-Dong
最近的研究表明，饮食诱导的fractalkine （FKN）在肥胖动物模型中刺激神经炎症，但其发生机制尚不清楚。本研究探讨了FKN及其受体CX3CR1在果糖诱导的神经炎症中的作用，并考察了姜黄素的有益作用。研究发现，果糖喂养通过激活toll样受体4 (TLR4)/核转录因子κ B （nf - κ B）信号，诱导海马小胶质细胞活化并发生神经炎症，导致小鼠齿状回（DG）神经发生减少。果糖喂养的下丘脑小胶质细胞激活小鼠血清FKN水平以及下丘脑FKN和CX3CR1基因表达显著升高。果糖喂养小鼠海马FKN和CX3CR1基因表达在14 d时上调，在56 d时正常化，与GFAP的变化一致。此外，免疫染色结果显示，在果糖喂养的小鼠中，玉米1中GFAP和FKN的表达增加，而DG中GFAP和FKN的表达降低。体外研究表明，星形胶质细胞中GFAP和FKN的表达受到刺激，48 h-果糖混合胶质细胞中GFAP和FKN的表达受到抑制，促炎细胞因子不断增加。因此，FKN和CX3CR1的增加可能引起活化的胶质细胞和神经元之间的串扰，在果糖喂养小鼠神经炎症的发展中起重要作用。姜黄素通过抑制小胶质细胞的激活和抑制神经元网络中FKN/CX3CR1的上调来保护果糖喂养小鼠海马DG的神经元损伤。这些结果提示了一种新的治疗方法来保护与饮食肥胖相关的神经炎症相关的神经元损伤。(C) 2016 Elsevier Inc.版权所有。
Recent studies suggest that diet-induced fractalkine (FKN) stimulates neuroinflammation in animal models of obesity, yet how it occurs is unclear. This study investigated the role of FKN and it receptor, CX3CR1, in fructose-induced neuroinflammation, and examined curcumin's beneficial effect. Fructose feeding was found to induce hippocampal microglia activation with neuroinflammation through the activation of the Toll-like receptor 4 (TLR4)/nuclear transcription factor kappa B (NF-kappa B) signaling, resulting in the reduction of neurogenesis in the dentate gyrus (DG) of mice. Serum FKN levels, as well as hypothalamic FKN and CX3CR1 gene expression, were significantly increased in fructose-fed mice with hypothalamic microglia activation. Hippocampal gene expression of FKN and CX3CR1 was also up-regulated at 14 d and normalized at 56 d in mice fed with fructose, which were consistent with the change of GFAP. Furthermore, immunostaining showed that GFAP and FKN expression was increased in cornu amonis 1, but decreased in DG in fructose-fed mice. In vitro studies showed that GFAP and FKN expression was stimulated in astrocytes, and suppressed in mixed glial cells exposed to 48 h-fructose, with the continual increase of pro-inflammatory cytokines. Thus, increased FKN and CX3CR1 may cause a cross-talk between activated glial cells and neurons, playing an important role in the development of neuroinflammation in fructose fed mice. Curcumin protected against neuronal damage in hippocampal DG of fructose-fed mice by inhibiting microglia activation and suppressed FKN/CX3CR1 up-regulation in the neuronal network. These results suggest a new therapeutic approach to protect against neuronal damage associated with dietary obesity-associated neuroinflammation. (C) 2016 Elsevier Inc. All rights reserved.