Tilleux Sébastien, Hermans Emmanuel
Laboratoire de Pharmacologie Expérimentale, Faculté de Médecine, Université catholique de Louvain, Brussels, Belgium.
J Neurosci Res. 2007 Aug 1;85(10):2059-70. doi: 10.1002/jnr.21325.
Oxidative stress, neuroinflammation, and excitotoxicity are frequently considered distinct but common hallmarks of several neurological disorders, including Parkinson's disease, amyotrophic lateral sclerosis, multiple sclerosis, and Alzheimer's disease. Although neuron degeneration and death are the ultimate consequences of these pathological processes, it is now widely accepted that alterations in the function of surrounding glial cells are key features in the progression of these diseases. In response to alteration in their local environment, microglia, commonly considered the resident immune cells of the nervous parenchyma, become activated and release a variety of soluble factors. Among these, proinflammatory cytokines and free radicals actively participate in the degenerative insults. In addition, excitotoxic neuronal damage resulting from excessive glutamate is frequently associated with impaired handling of extracellular glutamate by gliotic astrocytes. Although several research projects have focused on the biochemical mechanisms of the regulation of glial glutamate transporters, a relationship between activation of microglia and modulation of astrocytic glutamate uptake is now suggested. The aim of this review is to summarize and discuss the data showing an influence of inflammatory mediators and related free radicals on the expression and activity of glial glutamate transporters.
氧化应激、神经炎症和兴奋性毒性常被视为几种神经疾病（包括帕金森病、肌萎缩侧索硬化症、多发性硬化症和阿尔茨海默病）不同但常见的特征。尽管神经元变性和死亡是这些病理过程的最终结果，但现在人们普遍认为，周围神经胶质细胞功能的改变是这些疾病进展的关键特征。作为对局部环境变化的反应，通常被认为是神经实质内驻留免疫细胞的小胶质细胞被激活并释放多种可溶性因子。其中，促炎细胞因子和自由基积极参与退行性损伤。此外，过量谷氨酸导致的兴奋性毒性神经元损伤通常与胶质化星形胶质细胞对细胞外谷氨酸的处理受损有关。尽管有几个研究项目聚焦于胶质谷氨酸转运体调控的生化机制，但现在有人提出小胶质细胞激活与星形胶质细胞谷氨酸摄取调节之间存在关联。本综述的目的是总结和讨论显示炎症介质及相关自由基对胶质谷氨酸转运体表达和活性有影响的数据。
