CXCR4-activated astrocyte glutamate release via TNFalpha: amplification by microglia triggers neurotoxicity.

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作者：

P Bezzi，M Domercq，L Brambilla，R Galli，Andrea Volterra

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摘要：

Astrocytes actively participate in synaptic integration by releasing transmitter () via a calcium-regulated, -like process. Here we show that this process follows activation of the receptor by the chemokine stromal cell-derived factor 1 (). An extraordinary feature of the ensuing signaling cascade is the rapid release of -alpha (). Autocrine/paracrine -dependent signaling leading to (PG) formation not only controls release and astrocyte communication, but also causes their derangement when activated microglia cooperate to dramatically enhance release of the cytokine in response to stimulation. We demonstrate that altered glial communication has direct neuropathological consequences and that agents interfering with -dependent astrocyte-microglia signaling prevent neuronal induced by the coat , gp120IIIB. Our results identify a new pathway for glia-glia and glia-neuron communication that is relevant to both normal brain function and .

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关键词：

Astrocytes Glutamic Acid Microglia Receptors, CXCR4 Tumor Necrosis Factor 星形细胞谷氨酸小神经胶质细胞受体, CXCR4 肿瘤坏死因子