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Cited by 964

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

Bezzi, Paola, Domercq, Maria, Brambilla, Liliana, Galli, Rossella, Schols, Dominique, De Clercq, Erik, Vescovi, Angelo, Bagetta, Giacinto +3 more·2001·Nature Neuroscience
DOI 10.1038/89490
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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.

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Crossref · 10.1038/89490

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  • TNF-α can potentiate glutamate-mediated cytotoxicity by indirectly inhibiting glutamate transport on astrocytes and directly stimulating microglial and/or astrocyte glutamate release in an autocrine manner.

    “For instance, TNF-α can potentiate glutamate-mediated cytotoxicity by two complementary mechanisms: indirectly, by inhibiting glutamate transport on astrocytes, and directly, by stimulating extensive microglial and/or astrocyte glutamate release in an autocrine manner.”

    From TNF-alpha-induced microglia activation requires miR-342: Impact on NF-kB signaling and neurotoxicity (2020) · cites this paper as [43]

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Authors
Bezzi, P., Domercq, M., Brambilla, L., Galli, R., Schols, D., De Clercq, E., Vescovi, A., Bagetta, G., Kollias, G., Meldolesi, J., & Volterra, A.
Venue
Nature Neuroscience
Publisher
Springer Science and Business Media LLC
Published
2001-07
Volume
4
Issue
7
Pages
702-710
ISSN
  • 1097-6256
  • 1546-1726
DOI
10.1038/89490
Cited by
964
References
0
Language
en
Licence
www.springer.com/tdm (tdm)

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