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Titolo:
CXCR4-activated astrocyte glutamate release via TNFa: amplification by microglia triggers neurotoxicity
Autore:
Bezzi, P; Domercq, M; Brambilla, L; Galli, R; Schols, D; De Clercq, E; Vescovi, A; Bagetta, G; Kollias, G; Meldolesi, J; Volterra, A;
Indirizzi:
Univ Milan, Ctr Excellence Neurodegenerat Dis, Dept Pharmacol Sci, I-20133Milan, Italy Univ Milan Milan Italy I-20133 , Dept Pharmacol Sci, I-20133Milan, Italy San Raffaele Sci Inst, Dept Neurosci, DIBIT, I-20132 Milan, Italy San Raffaele Sci Inst Milan Italy I-20132 i, DIBIT, I-20132 Milan, Italy Vita Salute Univ, I-20132 Milan, Italy Vita Salute Univ Milan Italy I-20132 a Salute Univ, I-20132 Milan, Italy Hosp San Raffaele, Stem Cell Res Inst, I-20132 Milan, Italy Hosp San Raffaele Milan Italy I-20132 ell Res Inst, I-20132 Milan, Italy Katholieke Univ Leuven, Rega Inst Med Res, B-3000 Louvain, Belgium Katholieke Univ Leuven Louvain Belgium B-3000 s, B-3000 Louvain, Belgium Univ Calabria, Dept Pharmacobiol, I-87036 Cosenza, Italy Univ Calabria Cosenza Italy I-87036 Pharmacobiol, I-87036 Cosenza, Italy Biomed Sci Res Ctr Al Fleming, Inst Immunol, Vari 16672, Greece Biomed SciRes Ctr Al Fleming Vari Greece 16672 unol, Vari 16672, Greece
Titolo Testata:
NATURE NEUROSCIENCE
fascicolo: 7, volume: 4, anno: 2001,
pagine: 702 - 710
SICI:
1097-6256(200107)4:7<702:CAGRVT>2.0.ZU;2-0
Fonte:
ISI
Lingua:
ENG
Soggetto:
CULTURED HIPPOCAMPAL-NEURONS; COAT PROTEIN GP120; GLIAL-CELLS; SYNAPTIC TRANSMISSION; SIGNAL-TRANSDUCTION; CHEMOKINE RECEPTORS; IN-SITU; CXCR4; MODULATION; ALPHA;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
50
Recensione:
Indirizzi per estratti:
Indirizzo: Volterra, A Univ Milan, Ctr Excellence Neurodegenerat Dis, Dept Pharmacol Sci, Via Balzaretti 9, I-20133 Milan, Italy Univ Milan Via Balzaretti 9 Milan Italy I-20133 Milan, Italy
Citazione:
P. Bezzi et al., "CXCR4-activated astrocyte glutamate release via TNFa: amplification by microglia triggers neurotoxicity", NAT NEUROSC, 4(7), 2001, pp. 702-710

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 (TNF alpha). Autocrine/paracrine TNF alpha -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, gp120(IIIB) Our resultsidentify a new pathway for glia-glia and glia-neuron communication that isrelevant to both normal brain function and neurodegenerative diseases.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 19/01/20 alle ore 00:32:36