@article{ebc2d1901ca111df8ed1000ea68e967b,
title = "CXCL10/CXCR3 signaling in glia cells differentially affects NMDA-induced cell death in CA and DG neurons of the mouse hippocampus",
abstract = "The chemokine CXCL10 and its receptor CXCR3 are implicated in various CNS pathologies since interference with CXCL10/CXCR3 signaling alters the onset and progression in various CNS disease models. However, the mechanism and cell-types involved in CXCL10/CXCR3 signaling under pathological conditions are far from understood. Here, we investigated the potential role for CXCL10/CXCR3 signaling in neuronal cell death and glia activation in response to N-methyl-D-aspartic acid (NMDA)-induced excitotoxicity in mouse organotypic hippocampal slice cultures (OHSCs). Our findings demonstrate that astrocytes express CXCL10 in response to excitotoxicity. Experiments in OHSCs derived from CXCL10-deficient (CXCL10-/-) and CXCR3-deficient (CXCR3-/-) revealed that in the absence of CXCL10 or CXCR3, neuronal cell death in the CA1 and CA3 regions was diminished after NMDA-treatment when compared to wild type OHSCs. In contrast, neuronal cell death in the DG region was enhanced in both CXCL10-/- and CXCR3-/- OHSCs in response to a high (50 μM) NMDA-concentration. Moreover, we show that in the absence of microglia the differential changes in neuronal vulnerability between CXCR3-/- and wild type OHSCs are fully abrogated and therefore a prominent role for microglia in this process is suggested. Taken together, our results identify a region-specific role for CXCL10/CXCR3 signaling in neuron-glia and glia-glia interactions under pathological conditions.",
author = "{van Weering}, {Hilmar R J} and Boddeke, {Hendrikus W G M} and Jonathan Vinet and Nieske Brouwer and {de Haas}, {Alexander H} and {van Rooijen}, Nico and Thomsen, {Allan R} and Biber, {Knut P H}",
year = "2011",
month = feb,
doi = "10.1002/hipo.20742",
language = "English",
journal = "Hippocampus",
issn = "1050-9631",
publisher = "JohnWiley & Sons, Inc.",
}