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Cannabinoids and neuronal damage: differential effects of THC, AEA and 2-AG on activated microglial cells and degenerating neurons in excitotoxically lesioned rat organotypic hippocampal slice cultures.
Exp Neurol. 2007 Jan; 203(1):246-57.EN

Abstract

Cannabinoids (CBs) are attributed neuroprotective effects in vivo. Here, we determined the neuroprotective potential of CBs during neuronal damage in excitotoxically lesioned organotypic hippocampal slice cultures (OHSCs). OHSCs are the best characterized in vitro model to investigate the function of microglial cells in neuronal damage since blood-borne monocytes and T-lymphocytes are absent and microglial cells represent the only immunocompetent cell type. Excitotoxic neuronal damage was induced by NMDA (50 microM) application for 4 h. Neuroprotective properties of 9-carboxy-11-nor-delta-9-tetrahydrocannabinol (THC), N-arachidonoylethanolamide (AEA) or 2-arachidonoylglycerol (2-AG) in different concentrations were determined after co-application with NMDA by counting degenerating neurons identified by propidium iodide labeling (PI(+)) and microglial cells labeled by isolectin B(4) (IB(4)(+)). All three CBs used significantly decreased the number of IB(4)(+) microglial cells in the dentate gyrus but the number of PI(+) neurons was reduced only after 2-AG treatment. Application of AM630, antagonizing CB2 receptors highly expressed by activated microglial cells, did not counteract neuroprotective effects of 2-AG, but affected THC-mediated reduction of IB(4)(+) microglial cells. Our results indicate that (1) only 2-AG exerts neuroprotective effects in OHSCs; (2) reduction of IB(4)(+) microglial cells is not a neuroprotective event per se and involves other CB receptors than the CB2 receptor; (3) the discrepancy in the neuroprotective effects of CBs observed in vivo and in our in vitro model system may underline the functional relevance of invading monocytes and T-lymphocytes that are absent in OHSCs.

Authors+Show Affiliations

Dr. Senckenbergische Anatomie, Institut für Anatomie 2, Johann Wolfgang Goethe-Universität Frankfurt, Theodor-Stern-Kai 7, 60590 Frankfurt/Main, Germany.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

17010339

Citation

Kreutz, Susanne, et al. "Cannabinoids and Neuronal Damage: Differential Effects of THC, AEA and 2-AG On Activated Microglial Cells and Degenerating Neurons in Excitotoxically Lesioned Rat Organotypic Hippocampal Slice Cultures." Experimental Neurology, vol. 203, no. 1, 2007, pp. 246-57.
Kreutz S, Koch M, Ghadban C, et al. Cannabinoids and neuronal damage: differential effects of THC, AEA and 2-AG on activated microglial cells and degenerating neurons in excitotoxically lesioned rat organotypic hippocampal slice cultures. Exp Neurol. 2007;203(1):246-57.
Kreutz, S., Koch, M., Ghadban, C., Korf, H. W., & Dehghani, F. (2007). Cannabinoids and neuronal damage: differential effects of THC, AEA and 2-AG on activated microglial cells and degenerating neurons in excitotoxically lesioned rat organotypic hippocampal slice cultures. Experimental Neurology, 203(1), 246-57.
Kreutz S, et al. Cannabinoids and Neuronal Damage: Differential Effects of THC, AEA and 2-AG On Activated Microglial Cells and Degenerating Neurons in Excitotoxically Lesioned Rat Organotypic Hippocampal Slice Cultures. Exp Neurol. 2007;203(1):246-57. PubMed PMID: 17010339.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Cannabinoids and neuronal damage: differential effects of THC, AEA and 2-AG on activated microglial cells and degenerating neurons in excitotoxically lesioned rat organotypic hippocampal slice cultures. AU - Kreutz,Susanne, AU - Koch,Marco, AU - Ghadban,Chalid, AU - Korf,Horst-Werner, AU - Dehghani,Faramarz, Y1 - 2006/09/27/ PY - 2006/06/22/received PY - 2006/08/07/revised PY - 2006/08/10/accepted PY - 2006/10/3/pubmed PY - 2007/2/24/medline PY - 2006/10/3/entrez SP - 246 EP - 57 JF - Experimental neurology JO - Exp Neurol VL - 203 IS - 1 N2 - Cannabinoids (CBs) are attributed neuroprotective effects in vivo. Here, we determined the neuroprotective potential of CBs during neuronal damage in excitotoxically lesioned organotypic hippocampal slice cultures (OHSCs). OHSCs are the best characterized in vitro model to investigate the function of microglial cells in neuronal damage since blood-borne monocytes and T-lymphocytes are absent and microglial cells represent the only immunocompetent cell type. Excitotoxic neuronal damage was induced by NMDA (50 microM) application for 4 h. Neuroprotective properties of 9-carboxy-11-nor-delta-9-tetrahydrocannabinol (THC), N-arachidonoylethanolamide (AEA) or 2-arachidonoylglycerol (2-AG) in different concentrations were determined after co-application with NMDA by counting degenerating neurons identified by propidium iodide labeling (PI(+)) and microglial cells labeled by isolectin B(4) (IB(4)(+)). All three CBs used significantly decreased the number of IB(4)(+) microglial cells in the dentate gyrus but the number of PI(+) neurons was reduced only after 2-AG treatment. Application of AM630, antagonizing CB2 receptors highly expressed by activated microglial cells, did not counteract neuroprotective effects of 2-AG, but affected THC-mediated reduction of IB(4)(+) microglial cells. Our results indicate that (1) only 2-AG exerts neuroprotective effects in OHSCs; (2) reduction of IB(4)(+) microglial cells is not a neuroprotective event per se and involves other CB receptors than the CB2 receptor; (3) the discrepancy in the neuroprotective effects of CBs observed in vivo and in our in vitro model system may underline the functional relevance of invading monocytes and T-lymphocytes that are absent in OHSCs. SN - 0014-4886 UR - https://www.unboundmedicine.com/medline/citation/17010339/Cannabinoids_and_neuronal_damage:_differential_effects_of_THC_AEA_and_2_AG_on_activated_microglial_cells_and_degenerating_neurons_in_excitotoxically_lesioned_rat_organotypic_hippocampal_slice_cultures_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0014-4886(06)00480-8 DB - PRIME DP - Unbound Medicine ER -