Microglial activation is a major contributor to neurologic dysfunction in thiamine deficiency
Microglial activation is a major contributor to neurologic dysfunction in thiamine deficiency
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DOI：
10.1016/j.bbrc.2010.09.128
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发表时间：
2010-11-05
影响因子：
3.1
通讯作者：
Hazel, Alan S.
中科院分区：
文献类型：
--
作者：
Wang, Dongmei;Hazel, Alan S.
在韦尼克脑病和硫胺素缺乏症(TD)中，炎症的发展是疾病过程中的一个重要方面，是导致这种脑部疾病的原因。然而，这种病理机制如何与TD相关的神经损害有关仍不清楚。炎症过程的一个关键特征是小胶质细胞的激活。在本研究中，我们通过检测与小胶质细胞激活相关的两种蛋白CD11b/c和CD68的水平与TD神经功能障碍之间的关系，来评价小胶质细胞激活在TD病理生理学中的作用。TD大鼠易损丘脑和下丘中CD11b/c和CD68的表达均显著增加，而相对非易损的额叶皮质中CD11b/c和CD68的表达无明显变化。CD11b/c和CD68表达的这些变化反映在免疫印迹和免疫组织化学方法这两种蛋白的显著上调上。与单独使用TD的动物相比，TD和抗炎药物米诺环素联合治疗可以阻止小胶质细胞的激活，并且包括翻正反射丧失在内的神经变化的开始时间推迟了大约39小时。此外，TD和N-乙酰半胱氨酸联合治疗可阻止CD11b/c和CD68的增加，但不能改变神经损伤的发生。这些结果表明，小胶质细胞的激活在TD和可能的WerNicke脑病的神经功能损害的发展中发挥了作用，虽然氧化应激的发展可能涉及小胶质细胞的激活，但这种神经功能障碍的基础可能是多因素的。(C)2010 Elsevier Inc.保留所有权利。
In Wernicke's encephalopathy and thiamine deficiency (TD), the cause of this brain disorder, development of inflammation is an important aspect of the disease process. How this pathological mechanism relates to the neurologic impairment associated with TD, however, remains unclear. A key feature of the inflammatory process is the activation of microglia. In the present study, we evaluated the role of microglial activation in the pathophysiology of TD by examining the relationship between levels of CD11b/c and CD68, two proteins associated with microglial activation, and neurological dysfunction under conditions of TD. Rats with TD showed large increases in expression of both CD11b/c and CD68 in the vulnerable thalamus and inferior colliculus, with no change in mRNA levels in the relatively non-vulnerable frontal cortex. These alterations in CD11b/c and CD68 expression were reflected in dramatic upregulation of both proteins by immunoblotting and immunohistochemical methods. Co-treatment of rats with TD and the anti-inflammatory drug minocycline prevented microglial activation, and onset of neurological changes, including loss of righting reflex, was delayed by approximately 39 h, compared to animals with TD alone. In addition, co-treatment of rats with TD and N-acetylcysteine prevented the increase in CD11b/c and CD68, but did not alter the onset of neurological impairment. These results suggest that microglial activation plays a role in the development of neurological impairment in TD and possibly Wernicke's encephalopathy, and that while development of oxidative stress may be involved in microglial activation, the basis of this neurologic dysfunction is likely to be multifactorial in nature. (C) 2010 Elsevier Inc. All rights reserved.