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THC (Δ9-Tetrahydrocannabinol) Exerts Neuroprotective Effect in Glutamate-affected Murine Primary Mesencephalic Cultures Through Restoring Mitochondrial Membrane Potential and Anti-apoptosis Involving CB1 Receptor-dependent Mechanism.
Phytother Res. 2016 Dec; 30(12):2044-2052.PR

Abstract

Aging-related neurodegenerative diseases, such as Parkinson's disease (PD) or related disorders, are an increasing societal and economic burden worldwide. Δ9-Tetrahydrocannabinol (THC) is discussed as a neuroprotective agent in several in vitro and in vivo models of brain injury. However, the mechanisms by which THC exhibits neuroprotective properties are not completely understood. In the present study, we investigated neuroprotective mechanisms of THC in glutamate-induced neurotoxicity in primary murine mesencephalic cultures, as a culture model for PD. Glutamate was administered for 48 h with or without concomitant THC treatment. Immunocytochemistry staining and resazurin assay were used to evaluate cell viability. Furthermore, superoxide levels, caspase-3 activity, and mitochondrial membrane potential were determined to explore the mode of action of this compound. THC protected dopaminergic neurons and other cell types of primary dissociated cultures from glutamate-induced neurotoxicity. Moreover, THC significantly counteracted the glutamate-induced mitochondrial membrane depolarization and apoptosis. SR141716A, a CB1 receptor antagonist, concentration-dependently blocked the protective effect of THC in primary mesencephalic cultures. In conclusion, THC exerts anti-apoptotic and restores mitochondrial membrane potential via a mechanism dependent on CB1 receptor. It strengthens the fact that THC has a benefit on degenerative cellular processes occurring, among others, in PD and other neurodegenerative diseases by slowing down the progression of neuronal cell death. Copyright © 2016 John Wiley & Sons, Ltd.

Authors+Show Affiliations

Institute for Medical Biochemistry, University of Veterinary Medicine, Veterinaerplatz 1, A-1210, Vienna, Austria.Institute for Medical Biochemistry, University of Veterinary Medicine, Veterinaerplatz 1, A-1210, Vienna, Austria.Department of Pathology, Faculty of Veterinary Medicine, Assiut University, Assiut, Egypt.Institute for Medical Biochemistry, University of Veterinary Medicine, Veterinaerplatz 1, A-1210, Vienna, Austria.Institute for Medical Biochemistry, University of Veterinary Medicine, Veterinaerplatz 1, A-1210, Vienna, Austria.Institute for Medical Biochemistry, University of Veterinary Medicine, Veterinaerplatz 1, A-1210, Vienna, Austria.Institute for Medical Biochemistry, University of Veterinary Medicine, Veterinaerplatz 1, A-1210, Vienna, Austria.Institute for Medical Biochemistry, University of Veterinary Medicine, Veterinaerplatz 1, A-1210, Vienna, Austria.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

27654887

Citation

Nguyen, Chi Huu, et al. "THC (Δ9-Tetrahydrocannabinol) Exerts Neuroprotective Effect in Glutamate-affected Murine Primary Mesencephalic Cultures Through Restoring Mitochondrial Membrane Potential and Anti-apoptosis Involving CB1 Receptor-dependent Mechanism." Phytotherapy Research : PTR, vol. 30, no. 12, 2016, pp. 2044-2052.
Nguyen CH, Krewenka C, Radad K, et al. THC (Δ9-Tetrahydrocannabinol) Exerts Neuroprotective Effect in Glutamate-affected Murine Primary Mesencephalic Cultures Through Restoring Mitochondrial Membrane Potential and Anti-apoptosis Involving CB1 Receptor-dependent Mechanism. Phytother Res. 2016;30(12):2044-2052.
Nguyen, C. H., Krewenka, C., Radad, K., Kranner, B., Huber, A., Duvigneau, J. C., Miller, I., & Moldzio, R. (2016). THC (Δ9-Tetrahydrocannabinol) Exerts Neuroprotective Effect in Glutamate-affected Murine Primary Mesencephalic Cultures Through Restoring Mitochondrial Membrane Potential and Anti-apoptosis Involving CB1 Receptor-dependent Mechanism. Phytotherapy Research : PTR, 30(12), 2044-2052. https://doi.org/10.1002/ptr.5712
Nguyen CH, et al. THC (Δ9-Tetrahydrocannabinol) Exerts Neuroprotective Effect in Glutamate-affected Murine Primary Mesencephalic Cultures Through Restoring Mitochondrial Membrane Potential and Anti-apoptosis Involving CB1 Receptor-dependent Mechanism. Phytother Res. 2016;30(12):2044-2052. PubMed PMID: 27654887.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - THC (Δ9-Tetrahydrocannabinol) Exerts Neuroprotective Effect in Glutamate-affected Murine Primary Mesencephalic Cultures Through Restoring Mitochondrial Membrane Potential and Anti-apoptosis Involving CB1 Receptor-dependent Mechanism. AU - Nguyen,Chi Huu, AU - Krewenka,Christopher, AU - Radad,Khaled, AU - Kranner,Barbara, AU - Huber,Alexandra, AU - Duvigneau,Johanna Catharina, AU - Miller,Ingrid, AU - Moldzio,Rudolf, Y1 - 2016/09/22/ PY - 2016/06/14/received PY - 2016/08/05/revised PY - 2016/08/17/accepted PY - 2016/9/23/pubmed PY - 2017/3/31/medline PY - 2016/9/23/entrez KW - THC KW - anti-apoptosis KW - glutamate KW - mesencephalic culture KW - neuroprotection KW - neurotoxicity SP - 2044 EP - 2052 JF - Phytotherapy research : PTR JO - Phytother Res VL - 30 IS - 12 N2 - Aging-related neurodegenerative diseases, such as Parkinson's disease (PD) or related disorders, are an increasing societal and economic burden worldwide. Δ9-Tetrahydrocannabinol (THC) is discussed as a neuroprotective agent in several in vitro and in vivo models of brain injury. However, the mechanisms by which THC exhibits neuroprotective properties are not completely understood. In the present study, we investigated neuroprotective mechanisms of THC in glutamate-induced neurotoxicity in primary murine mesencephalic cultures, as a culture model for PD. Glutamate was administered for 48 h with or without concomitant THC treatment. Immunocytochemistry staining and resazurin assay were used to evaluate cell viability. Furthermore, superoxide levels, caspase-3 activity, and mitochondrial membrane potential were determined to explore the mode of action of this compound. THC protected dopaminergic neurons and other cell types of primary dissociated cultures from glutamate-induced neurotoxicity. Moreover, THC significantly counteracted the glutamate-induced mitochondrial membrane depolarization and apoptosis. SR141716A, a CB1 receptor antagonist, concentration-dependently blocked the protective effect of THC in primary mesencephalic cultures. In conclusion, THC exerts anti-apoptotic and restores mitochondrial membrane potential via a mechanism dependent on CB1 receptor. It strengthens the fact that THC has a benefit on degenerative cellular processes occurring, among others, in PD and other neurodegenerative diseases by slowing down the progression of neuronal cell death. Copyright © 2016 John Wiley & Sons, Ltd. SN - 1099-1573 UR - https://www.unboundmedicine.com/medline/citation/27654887/THC__Δ9_Tetrahydrocannabinol__Exerts_Neuroprotective_Effect_in_Glutamate_affected_Murine_Primary_Mesencephalic_Cultures_Through_Restoring_Mitochondrial_Membrane_Potential_and_Anti_apoptosis_Involving_CB1_Receptor_dependent_Mechanism_ L2 - https://doi.org/10.1002/ptr.5712 DB - PRIME DP - Unbound Medicine ER -