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Protective Effect of N-Arachidonoyl Glycine-GPR18 Signaling after Excitotoxical Lesion in Murine Organotypic Hippocampal Slice Cultures

Institute of Anatomy and Cell Biology, Medical Faculty of Martin Luther University Halle-Wittenberg, Grosse Steinstrasse 52, 06108 Halle (Saale), Germany
Biomedical Materials Group, Institute of Pharmacy & Interdisciplinary Center for Materials Science, Martin Luther University Halle-Wittenberg, Heinrich-Damerow Strasse 4, 06120 Halle (Saale), Germany
Department of Psychological & Brain Sciences, Indiana University, 1101 E. 10th, Bloomington, IN 47405, USA
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2019, 20(6), 1266;
Received: 24 January 2019 / Revised: 6 March 2019 / Accepted: 9 March 2019 / Published: 13 March 2019
(This article belongs to the Special Issue Neuroinflammation and Cell Death)
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N-arachidonoyl glycine (NAGly) is an endocannabinoid involved in the regulation of different immune cells. It was shown to activate the GPR18 receptor, which was postulated to switch macrophages from cytotoxic to reparative. To study GPR18 expression and neuroprotection after NAGly treatment we used excitotoxically lesioned organotypic hippocampal slice cultures (OHSC). The effect of NAGly was also tested in isolated microglia and astrocytes as these cells play a crucial role during neuronal injury. In the present study, the GPR18 receptor was found in OHSC at mRNA level and was downregulated after N-Methyl-D-aspartate (NMDA) treatment at a single time point. Furthermore, treatment with NAGly reduced neuronal damage and this effect was abolished by GPR18 and cannabinoid receptor (CB)2 receptor antagonists. The activation but not motility of primary microglia and astrocytes was influenced when incubated with NAGly. However, NAGly alone reduced the phosphorylation of Akt but no changes in activation of the p44/42 and p38 MAPK and CREB pathways in BV2 cells could be observed. Given NAGly mediated actions we speculate that GPR18 and its ligand NAGly are modulators of glial and neuronal cells during neuronal damage. View Full-Text
Keywords: microglia; neuroprotection; N-arachidonoyl glycine microglia; neuroprotection; N-arachidonoyl glycine

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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).

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Grabiec, U.; Hohmann, T.; Ghadban, C.; Rothgänger, C.; Wong, D.; Antonietti, A.; Groth, T.; Mackie, K.; Dehghani, F. Protective Effect of N-Arachidonoyl Glycine-GPR18 Signaling after Excitotoxical Lesion in Murine Organotypic Hippocampal Slice Cultures. Int. J. Mol. Sci. 2019, 20, 1266.

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