Neuroprotective activity of chemokines against N-methyl-D-aspartate or beta-amyloid-induced toxicity in culture

We have examined the effect of various chemokines on neuronal toxicity in c ulture. In mixed cortical cultures, challenged with a brief pulse of N-meth yl-D-aspartate (NMDA, 60 mu M, 10 min), chemokines were either present for 2 h preceding the pulse or they were co-applied with NMDA and then kept in the medium for the following 20-24 h. Interleukin-8 (IL-8), regulated on ac tivation of normal T cells expressed and secreted (RANTES) and macrophage/m onocyte chemoattractant protein-1 (MCP-I), were neuroprotective under both conditions, whereas stromal cell-derived factor 1 alpha (SDF-1 alpha) was p rotective only when applied during and after the NMDA pulse. Mixed or pure neuronal cultures were also exposed for 48 h to a toxic fragment of the bet a-amyloid peptide (beta-amyloid peptide-(25-35), 12.5 or 25 mu M) in the ab sence or presence of chemokines. Among a number of chemokines, only RANTES was neuroprotective against beta-amyloid peptide-(25-35)-induced neurotoxic ity in both cultures. We conclude that activation of chemokine receptors di fferentially affects neuronal degeneration induced by excitotoxins or beta- amyloid peptide in cortical cultures. (C) 2000 Elsevier Science B.V. All ri ghts reserved.