Acetate supplementation reduces microglia activation and brain interleukin-1β levels in a rat model of Lyme neuroborreliosis.
Acetate supplementation reduces microglia activation and brain interleukin-1β levels in a rat model of Lyme neuroborreliosis.
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DOI：
10.1186/1742-2094-9-249
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发表时间：
2012-11-07
影响因子：
9.3
通讯作者：
Rosenberger TA
中科院分区：
文献类型：
--
作者：
Brissette CA;Houdek HM;Floden AM;Rosenberger TA
我们已经发现，在脂多糖诱导的神经炎症大鼠模型中，补充乙酸盐显著降低神经胶质细胞活化和促炎细胞因子释放。为了测试乙酸盐补充的抗炎作用是否特异于TLR 4介导的损伤，我们测量了经受B的大鼠中神经胶质细胞活化的标志物。伯氏螺旋体诱导的神经疏螺旋体病，其在很大程度上由TLR 2型机制介导。在这项研究中，大鼠在静脉输注B后发生莱姆神经疏螺旋体病。burgdorferi（B31-MI-16）。通过经口管饲法使用三乙酸甘油酯（6 g/kg）诱导乙酸酯补充。使用免疫组织化学、qPCR和蛋白质印迹分析来测量细菌侵入脑、神经胶质细胞活化以及白细胞介素1β的脑和循环水平。使用单因素方差分析（ANOVA）进行统计分析，然后进行Tukey事后检验或使用Student t检验（假设方差不等）（如适用）。我们发现，醋酸补充显着减少小胶质细胞激活2倍，免疫组化和蛋白质印迹分析确定。此外，与对照相比，乙酸盐补充还使促炎细胞因子IL-1β的表达降低2倍。另一方面，用B.通过免疫细胞化学和蛋白质印迹分析确定，尽管循环中B抗原水平显著增加，但Burgdorferi对星形胶质细胞活化没有影响。Burgdorferi和中枢神经系统中存在细菌。这些结果表明，小胶质细胞活化是神经疏螺旋体病的一个重要组成部分，醋酸补充剂可能是一种有效的治疗，以减少损伤表型和可能的损伤进展莱姆病神经疏螺旋体病。
We have found that acetate supplementation significantly reduces neuroglia activation and pro-inflammatory cytokine release in a rat model of neuroinflammation induced with lipopolysaccharide. To test if the anti-inflammatory effect of acetate supplementation is specific to a TLR4-mediated injury, we measured markers of neuroglia activation in rats subjected to B. burgdorferi-induced neuroborreliosis that is mediated in large part by a TLR2-type mechanism. In this study, rats were subjected to Lyme neuroborreliosis following an intravenous infusion of B. burgdorferi (B31-MI-16). Acetate supplementation was induced using glyceryl triacetate (6g/kg) by oral gavage. Immunohistochemistry, qPCR, and western blot analyses were used to measure bacterial invasion into the brain, neuroglial activation, and brain and circulating levels of interleukin 1β. Statistical analysis was performed using one-way analysis of variance (ANOVA) followed by a Tukey’s post hoc tests or using a Student’s t test assuming unequal variances when appropriate. We found that acetate supplementation significantly reduced microglia activation by 2-fold as determined by immunohistochemical and western blot analysis. Further, acetate supplementation also reduced the expression of the pro-inflammatory cytokine IL-1β by 2-fold as compared to controls. On the other hand, the inoculation of rats with B. burgdorferi had no effect on astroglial activation as determined by immunocytochemistry and western blot analysis despite significant increases in circulation levels of antigen toward B. burgdorferi and presence of the bacteria in the central nervous system. These results suggest that microglial activation is an essential component to neuroborreliosis and that acetate supplementation may be an effective treatment to reduce injury phenotype and possibly injury progression in Lyme neuroborreliosis.
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DOI：
10.1124/jpet.107.120188
发表时间：
2007-06-01
影响因子：
3.5
作者：
Kim, Hyeon Ju;Rowe, Michael;Chuang, De-Maw
通讯作者：
Chuang, De-Maw
影响因子：
3.1
作者：
Bernardino, Andrea L. F.;Myers, Tereance A.;Philipp, Mario T.
通讯作者：
Philipp, Mario T.
影响因子：
5.3
作者：
Rouaux, Caroline;Panteleeva, Irina;Loeffler, Jean-Philippe
通讯作者：
Loeffler, Jean-Philippe
影响因子：
4
作者：
Görisch, SM;Wachsmuth, M;Rippe, K
通讯作者：
Rippe, K
影响因子：
9.3
作者：
Ferger AI;Campanelli L;Reimer V;Muth KN;Merdian I;Ludolph AC;Witting A
通讯作者：
Witting A