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Protective Effect of N-Arachidonoyl Glycine-GPR18 Signaling after Excitotoxical Lesion in Murine Organotypic Hippocampal Slice Cultures.
Int J Mol Sci. 2019 Mar 13; 20(6)IJ

Abstract

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.

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Authors+Show Affiliations

Grabiec U
Institute of Anatomy and Cell Biology, Medical Faculty of Martin Luther University Halle-Wittenberg, Grosse Steinstrasse 52, 06108 Halle (Saale), Germany. urszula.grabiec@medizin.uni-halle.de.
Hohmann T
Institute of Anatomy and Cell Biology, Medical Faculty of Martin Luther University Halle-Wittenberg, Grosse Steinstrasse 52, 06108 Halle (Saale), Germany. tim.hohmann@medizin.uni-halle.de.
Ghadban C
Institute of Anatomy and Cell Biology, Medical Faculty of Martin Luther University Halle-Wittenberg, Grosse Steinstrasse 52, 06108 Halle (Saale), Germany. chalid.ghadban@medizin.uni-halle.de.
Rothgänger C
Institute of Anatomy and Cell Biology, Medical Faculty of Martin Luther University Halle-Wittenberg, Grosse Steinstrasse 52, 06108 Halle (Saale), Germany. candy.rothgaenger@medizin.uni-halle.de.
Wong D
Institute of Anatomy and Cell Biology, Medical Faculty of Martin Luther University Halle-Wittenberg, Grosse Steinstrasse 52, 06108 Halle (Saale), Germany. deagdeag@gmail.com.
Antonietti A
Institute of Anatomy and Cell Biology, Medical Faculty of Martin Luther University Halle-Wittenberg, Grosse Steinstrasse 52, 06108 Halle (Saale), Germany. alexandra_antonietti@yahoo.de.
Groth T
Biomedical Materials Group, Institute of Pharmacy & Interdisciplinary Center for Materials Science, Martin Luther University Halle-Wittenberg, Heinrich-Damerow Strasse 4, 06120 Halle (Saale), Germany. thomas.groth@pharmazie.uni-halle.de.
Mackie K
Department of Psychological & Brain Sciences, Indiana University, 1101 E. 10th, Bloomington, IN 47405, USA. kmackie@indiana.edu.
Dehghani F
Institute of Anatomy and Cell Biology, Medical Faculty of Martin Luther University Halle-Wittenberg, Grosse Steinstrasse 52, 06108 Halle (Saale), Germany. faramarz.dehghani@medizin.uni-halle.de.

MeSH

AnimalsArachidonic AcidsAstrocytesEndocannabinoidsGlycineHippocampusMiceMice, Inbred C57BLMicrogliaN-MethylaspartateNeuronsNeuroprotective AgentsReceptor, Cannabinoid, CB2Receptors, CannabinoidReceptors, G-Protein-CoupledSignal Transductionp38 Mitogen-Activated Protein Kinases

Pub Type(s)

Journal Article

Language

eng

PubMed ID

30871175

Citation

Grabiec, Urszula, et al. "Protective Effect of N-Arachidonoyl Glycine-GPR18 Signaling After Excitotoxical Lesion in Murine Organotypic Hippocampal Slice Cultures." International Journal of Molecular Sciences, vol. 20, no. 6, 2019.
Grabiec U, Hohmann T, Ghadban C, et al. Protective Effect of N-Arachidonoyl Glycine-GPR18 Signaling after Excitotoxical Lesion in Murine Organotypic Hippocampal Slice Cultures. Int J Mol Sci. 2019;20(6).
Grabiec, U., Hohmann, T., Ghadban, C., Rothgänger, C., Wong, D., Antonietti, A., Groth, T., Mackie, K., & Dehghani, F. (2019). Protective Effect of N-Arachidonoyl Glycine-GPR18 Signaling after Excitotoxical Lesion in Murine Organotypic Hippocampal Slice Cultures. International Journal of Molecular Sciences, 20(6). https://doi.org/10.3390/ijms20061266
Grabiec U, et al. Protective Effect of N-Arachidonoyl Glycine-GPR18 Signaling After Excitotoxical Lesion in Murine Organotypic Hippocampal Slice Cultures. Int J Mol Sci. 2019 Mar 13;20(6) PubMed PMID: 30871175.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Protective Effect of N-Arachidonoyl Glycine-GPR18 Signaling after Excitotoxical Lesion in Murine Organotypic Hippocampal Slice Cultures. AU - Grabiec,Urszula, AU - Hohmann,Tim, AU - Ghadban,Chalid, AU - Rothgänger,Candy, AU - Wong,Daniel, AU - Antonietti,Alexandra, AU - Groth,Thomas, AU - Mackie,Ken, AU - Dehghani,Faramarz, Y1 - 2019/03/13/ PY - 2019/01/24/received PY - 2019/03/06/revised PY - 2019/03/09/accepted PY - 2019/3/16/entrez PY - 2019/3/16/pubmed PY - 2019/6/27/medline KW - N-arachidonoyl glycine KW - microglia KW - neuroprotection JF - International journal of molecular sciences JO - Int J Mol Sci VL - 20 IS - 6 N2 - 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. SN - 1422-0067 UR - https://www.unboundmedicine.com/medline/citation/30871175/Protective_Effect_of_N_Arachidonoyl_Glycine_GPR18_Signaling_after_Excitotoxical_Lesion_in_Murine_Organotypic_Hippocampal_Slice_Cultures_ DB - PRIME DP - Unbound Medicine ER -