Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
7
pubmed:dateCreated
2001-6-26
pubmed:abstractText
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.
pubmed:commentsCorrections
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
1097-6256
pubmed:author
pubmed:issnType
Print
pubmed:volume
4
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
702-10
pubmed:dateRevised
2007-11-15
pubmed:meshHeading
pubmed-meshheading:11426226-Animals, pubmed-meshheading:11426226-Apoptosis, pubmed-meshheading:11426226-Astrocytes, pubmed-meshheading:11426226-Blotting, Western, pubmed-meshheading:11426226-Calcium, pubmed-meshheading:11426226-Cell Communication, pubmed-meshheading:11426226-Cells, Cultured, pubmed-meshheading:11426226-Chemokine CXCL12, pubmed-meshheading:11426226-Chemokines, CXC, pubmed-meshheading:11426226-Dinoprost, pubmed-meshheading:11426226-Extracellular Space, pubmed-meshheading:11426226-Glutamic Acid, pubmed-meshheading:11426226-HIV Envelope Protein gp120, pubmed-meshheading:11426226-Humans, pubmed-meshheading:11426226-Immunohistochemistry, pubmed-meshheading:11426226-Injections, Intraventricular, pubmed-meshheading:11426226-Mice, pubmed-meshheading:11426226-Mice, Mutant Strains, pubmed-meshheading:11426226-Microglia, pubmed-meshheading:11426226-Neocortex, pubmed-meshheading:11426226-Neurons, pubmed-meshheading:11426226-Rats, pubmed-meshheading:11426226-Receptors, CXCR4, pubmed-meshheading:11426226-Signal Transduction, pubmed-meshheading:11426226-Tumor Necrosis Factor-alpha
pubmed:year
2001
pubmed:articleTitle
CXCR4-activated astrocyte glutamate release via TNFalpha: amplification by microglia triggers neurotoxicity.
pubmed:affiliation
Department of Pharmacological Sciences, Center for Excellence on Neurodegenerative Diseases, University of Milan, Via Balzaretti, 9, 20133 Milan, Italy.
pubmed:publicationType
Journal Article, In Vitro, Research Support, Non-U.S. Gov't