Chronic caffeine treatment attenuates experimental autoimmune encephalomyelitis induced by guinea pig spinal cord homogenates in Wistar rats
Chronic caffeine treatment attenuates experimental autoimmune encephalomyelitis induced by guinea pig spinal cord homogenates in Wistar rats
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DOI：
10.1016/j.brainres.2009.10.054
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发表时间：
2010-01-14
期刊：
影响因子：
2.9
通讯作者：
Zheng, Rong Yuan
中科院分区：
文献类型：
--
作者：
Chen, Guo Qian;Chen, Yan Yan;Zheng, Rong Yuan
腺苷能系统的功能障碍与人类多发性硬化症和动物实验性自身免疫性脑脊髓炎（EAE）的发生有关。咖啡因是一种腺苷受体的非选择性拮抗剂，已被证明可提供对髓鞘少突胶质细胞的保护。糖蛋白（MOG）诱导的小鼠EAE。在这项研究中，我们表明，慢性咖啡因同样赋予神经保护作用，对EAE诱导的豚鼠脊髓匀浆（GPSCH）在大鼠。GPSCH诱导的EAE的特征在于具有典型慢性病程的广泛组织炎症。我们发现，咖啡因降低了EAE的发病率，并在行为、组织学（炎性细胞浸润和脱髓鞘）和神经化学（炎性细胞因子的表达）水平上减弱了EAE的病理学。在10和30 mg/kg剂量下以及在EAE的峰值和恢复阶段，观察到慢性咖啡因治疗对GPSCH诱导的病理学的衰减。此外，研究表明，咖啡因慢性治疗上调了EAE大鼠A1受体和TGF-β mRNA，并抑制了干扰素-γ mRNA。与以前的报告一起，我们的数据表明，长期使用咖啡因治疗对EAE产生神经保护作用，可能是通过A（1）受体介导的Th 1细胞功能向Th 2细胞功能的转变，并为流行病学调查提供了神经生物学基础咖啡因消费和人类多发性硬化症的发展之间的可能关系。(C)2009爱思唯尔有限公司版权所有。
Dysfunction of adenosinergic systems has been implicated in the development of multiple sclerosis in humans and experimental autoimmune encephalomyelitis (EAE) in animals. Caffeine, a non-selective antagonist of adenosine receptors, has been shown to provide protection against myelin oligodendroglia. glycoprotein (MOG)-induced EAE in mice. In this study, we showed that chronic caffeine similarly imparts neuroprotection against EAE induced in rats by guinea pig spinal cord homogenates (GPSCH). GPSCH-induced EAE is characterized by extensive tissue inflammation with a typical chronic disease course. We showed that caffeine decreases the incidence of EAE and attenuates EAE pathology at behavioral, histological (inflammatory cell infiltration and demyelination) and neurochemical (expression of inflammatory cytokines) levels. The attenuation of GPSCH-induced pathology by chronic caffeine treatment was observed at doses of 10 and 30 mg/kg and during both peak and recovery phases of EAE. Furthermore, it was showed that chronic treatment with caffeine up-regulated A1 receptor and TGF-beta mRNAs and suppressed interferon-gamma mRNA in EAE rats. Together with previous reports, our data demonstrates that chronic treatment with caffeine exerts a neuroprotective effect against EAE, possibly through an A(1) receptor-mediated shift from Th1 to Th2 cell function, and provides a neurobiological basis for epidemiological investigation into the possible relationship between caffeine consumption and development of multiple sclerosis in humans. (C) 2009 Elsevier B.V. All rights reserved.