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帕金森病神经毒性、环境及炎症大鼠模型中纹状体Toll样受体表达的时间进程。

Time-course of striatal Toll-like receptor expression in neurotoxic, environmental and inflammatory rat models of Parkinson's disease.

作者信息

McCabe Kiah, Concannon Ruth M, McKernan Declan P, Dowd Eilís

机构信息

Pharmacology & Therapeutics, National University of Ireland, Galway, Ireland; Galway Neuroscience Centre, National University of Ireland, Galway, Ireland.

Pharmacology & Therapeutics, National University of Ireland, Galway, Ireland; Galway Neuroscience Centre, National University of Ireland, Galway, Ireland.

出版信息

J Neuroimmunol. 2017 Sep 15;310:103-106. doi: 10.1016/j.jneuroim.2017.07.007. Epub 2017 Jul 13.

Abstract

Because Toll-like receptors (TLRs) are emerging as potential targets for anti-inflammatory intervention in neurodegenerative diseases, the aim of this study was to characterise the time-course of TLR expression in neurotoxic, environmental and inflammatory Parkinson's disease models. Male Sprague Dawley rats were given intra-striatal injections of 6-hydroxydopamine (10μg), rotenone (1.25μg), LPS (10μg) or Poly I:C (20μg) and were sacrificed on Days 1, 4, 14 and 28 post surgery. Changes in the expression of several inflammatory markers, including TLR3, TLR4 and selected cytokines, were examined using qRT-PCR. We found pronounced changes in the bacterial responsive TLR4 and the viral responsive TLR3 receptors in the inflamed striatum in all models, regardless of whether the challenge was neurotoxic, environmental or inflammatory in nature. However, the magnitude and time-course of changes in expression was different between the different models. This study highlights the pattern of changes in TLR expression in models of Parkinson's disease, and further strengthens the rationale for targeting TLRs for anti-inflammatory intervention in this neurodegenerative disease.

摘要

由于Toll样受体(TLRs)正逐渐成为神经退行性疾病抗炎干预的潜在靶点,本研究旨在描述神经毒性、环境性和炎症性帕金森病模型中TLR表达的时间进程。将雄性Sprague Dawley大鼠纹状体内注射6-羟基多巴胺(10μg)、鱼藤酮(1.25μg)、脂多糖(LPS,10μg)或聚肌苷酸:聚胞苷酸(Poly I:C,20μg),并在术后第1、4、14和28天处死。使用qRT-PCR检测包括TLR3、TLR4和选定细胞因子在内的几种炎症标志物表达的变化。我们发现,在所有模型中,无论刺激本质上是神经毒性、环境性还是炎症性的,炎症纹状体内细菌反应性TLR4和病毒反应性TLR3受体均有明显变化。然而,不同模型之间表达变化的幅度和时间进程有所不同。本研究突出了帕金森病模型中TLR表达的变化模式,并进一步强化了将TLRs作为该神经退行性疾病抗炎干预靶点的理论依据。

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