Toll 样受体 2 在吗啡诱导的小鼠小胶质细胞激活中的必需作用。
Essential role of toll-like receptor 2 in morphine-induced microglia activation in mice.
机构信息
Department of Internal Medicine, College of Medicine, East Tennessee State University, Johnson City, TN 37614, United States.
出版信息
Neurosci Lett. 2011 Feb 1;489(1):43-7. doi: 10.1016/j.neulet.2010.11.063. Epub 2010 Dec 2.
Abstract
Opioids are powerful pain relievers, but also potent inducers of dependence and tolerance. Chronic morphine administration (via subcutaneous pellet) induces morphine dependence in the nucleus accumbens, an important dependence region in the brain, yet the cellular mechanisms are mostly unknown. Toll-like receptor 2 (TLR2) plays an essential function in controlling innate and inflammatory responses. Using a knockout mouse lacking TLR2, we assessed the contribution of TLR2 to microglia activation and development of morphine dependence. We report here that mice deficient in TLR2 inhibit morphine-induced the levels of microglia activation and proinflammatory cytokines. Moreover, in TLR2 knockout mice the main symptoms of morphine withdrawal were significantly attenuated. Our data reveal that TLR2 plays a critical role in morphine-induced microglia activation and dependence.
摘要
阿片类药物是强效止痛药，但也是导致依赖和耐受的强效诱导剂。慢性吗啡给药（通过皮下植入丸）会在大脑中重要的依赖区域伏隔核中诱导吗啡依赖，但细胞机制在很大程度上尚不清楚。 Toll 样受体 2（TLR2）在控制先天和炎症反应中起着至关重要的作用。使用缺乏 TLR2 的基因敲除小鼠，我们评估了 TLR2 对小胶质细胞激活和吗啡依赖发展的贡献。我们在这里报告，缺乏 TLR2 的小鼠抑制了吗啡诱导的小胶质细胞激活和促炎细胞因子的水平。此外，TLR2 基因敲除小鼠的吗啡戒断的主要症状明显减轻。我们的数据表明，TLR2 在吗啡诱导的小胶质细胞激活和依赖中起着关键作用。
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