Title: CXCR4-activated astrocyte glutamate release via TNFalpha: amplification by microglia triggers neurotoxicity
Authors: Bezzi, P ×
Domercq, M
Brambilla, L
Galli, R
Schols, Dominique
De Clercq, Erik
Vescovi, A
Bagetta, G
Kollias, G
Meldolesi, J
Volterra, A #
Issue Date: Jul-2001
Series Title: Nature neuroscience vol:4 issue:7 pages:702-10
Abstract: Astrocytes actively participate in synaptic integration by releasing transmitter (glutamate) via a calcium-regulated, exocytosis-like process. Here we show that this process follows activation of the receptor CXCR4 by the chemokine stromal cell-derived factor 1 (SDF-1). An extraordinary feature of the ensuing signaling cascade is the rapid extracellular release of tumor necrosis factor-alpha (TNFalpha). Autocrine/paracrine TNFalpha-dependent signaling leading to prostaglandin (PG) formation not only controls glutamate release and astrocyte communication, but also causes their derangement when activated microglia cooperate to dramatically enhance release of the cytokine in response to CXCR4 stimulation. We demonstrate that altered glial communication has direct neuropathological consequences and that agents interfering with CXCR4-dependent astrocyte-microglia signaling prevent neuronal apoptosis induced by the HIV-1 coat glycoprotein, gp120IIIB. Our results identify a new pathway for glia-glia and glia-neuron communication that is relevant to both normal brain function and neurodegenerative diseases.
ISSN: 1097-6256
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Laboratory of Virology and Chemotherapy (Rega Institute)
× corresponding author
# (joint) last author

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