Modulation of synaptic functions by astrocytes

为了探索星形胶质细胞对神经递质的钙反应的变异性，我们检测了影响培养细胞钙反应模式的因素，并调查了切片制备过程中星形胶质细胞钙反应的后果。生长因子(表皮生长因子加碱性成纤维细胞生长因子)促进谷氨酸、三磷酸腺苷或硫柳汞(直接激活三磷酸肌醇受体)引起的钙振荡、钙库的扩大和肥大形态的发展，所有这些都是由丝裂原激活的蛋白激酶(MAPK)级联介导的。所有这三种作用都被促炎细胞因子(白介素1b或肿瘤坏死因子-a)、脂多糖或MAPK抑制剂U0126抑制，这表明影响脑功能和病理的因素对星形胶质细胞钙振荡的双重调节。在切片制备中，代谢型谷氨酸受体激动剂在神经元中诱导了类似的不依赖突触传递的钙振荡，表明星形胶质细胞的钙反应影响邻近神经元的活动，作为神经元活动的反馈机制。

To explore the variability in the calcium response of astrocytes to neurotransmitters, we examined factors affecting the pattern of calcium response in cultured cells and investigated the consequences of the astrocyte calcium response in slice preparations. Growth factors (epidermal growth factor plus basic fibroblast growth factor) promoted calcium oscillation in response to glutamate, ATP, or thimerosal (which directly activates the inositol-1, 4, 5 trisphosphate receptor), enlargement of the calcium store, and the development of a hypertrophic morphology, all of which were mediated by the mitogen-activated protein kinase (MAPK) cascade. All three effects were suppressed by proinflammatory cytokines (interleukin-1b or tumor necrosis factor-a), lipopolysaccharide, or a MAPK inhibitor, U0126 suggesting dual regulation of calcium oscillation in astrocytes by factors affecting brain function and pathology. In slice preparations, a metabotropic glutamate receptor agonist induced a similar calcium oscillation in neurons which was independent of synaptic transmission, indicating that the calcium response in astrocytes affects the activity of neighboring neurons as a feedback mechanism of neuronal activity.