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Effects of cannabinoids Δ(9)-tetrahydrocannabinol, Δ(9)-tetrahydrocannabinolic acid and cannabidiol in MPP+ affected murine mesencephalic cultures.
Phytomedicine. 2012 Jun 15; 19(8-9):819-24.P

Abstract

Cannabinoids derived from Cannabis sativa demonstrate neuroprotective properties in various cellular and animal models. Mitochondrial impairment and consecutive oxidative stress appear to be major molecular mechanisms of neurodegeneration. Therefore we studied some major cannabinoids, i.e. delta-9-tetrahydrocannabinolic acid (THCA), delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD) in mice mesencephalic cultures for their protective capacities against 1-methyl-4-phenyl pyridinium (MPP(+)) toxicity. MPP(+) is an established model compound in the research of parkinsonism that acts as a complex I inhibitor of the mitochondrial respiratory chain, resulting in excessive radical formation and cell degeneration. MPP(+) (10 μM) was administered for 48 h at the 9th DIV with or without concomitant cannabinoid treatment at concentrations ranging from 0.01 to 10 μM. All cannabinoids exhibited in vitro antioxidative action ranging from 669 ± 11.1 (THC), 16 ± 3.2 (THCA) to 356 ± 29.5 (CBD) μg Trolox (a vitamin E derivative)/mg substance in the 1,1-diphenyl-2-picrylhydrazyl radical (DPPH) assay. Cannabinoids were without effect on the morphology of dopaminergic cells stained by tyrosine hydroxylase (TH) immunoreaction. THC caused a dose-dependent increase of cell count up to 17.3% at 10 μM, whereas CBD only had an effect at highest concentrations (decrease of cell count by 10.1-20% at concentrations of 0.01-10 μM). It influenced the viability of the TH immunoreactive neurons significantly, whereas THCA exerts no influence on dopaminergic cell count. Exposure of cultures to 10 μM of MPP(+) for 48 h significantly decreased the number of TH immunoreactive neurons by 44.7%, and shrunken cell bodies and reduced neurite lengths could be observed. Concomitant treatment of cultures with cannabinoids rescued dopaminergic cells. Compared to MPP(+) treated cultures, THC counteracted toxic effects in a dose-dependent manner. THCA and CBD treatment at a concentration of 10 μM lead to significantly increased cell counts to 123% and 117%, respectively. Even though no significant preservation or recovery of neurite outgrowth to control values could be observed, our data show that cannabinoids THC and THCA protect dopaminergic neurons against MPP(+) induced cell death.

Authors+Show Affiliations

Institute of Chemistry and Biochemistry, Department for Biomedical Sciences, University for Veterinary Medicine, Veterinaerplatz 1, A-1210 Vienna, Austria. rudolf.moldzio@vetmeduni.ac.atNo affiliation info availableNo affiliation info availableNo 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

22571976

Citation

Moldzio, Rudolf, et al. "Effects of Cannabinoids Δ(9)-tetrahydrocannabinol, Δ(9)-tetrahydrocannabinolic Acid and Cannabidiol in MPP+ Affected Murine Mesencephalic Cultures." Phytomedicine : International Journal of Phytotherapy and Phytopharmacology, vol. 19, no. 8-9, 2012, pp. 819-24.
Moldzio R, Pacher T, Krewenka C, et al. Effects of cannabinoids Δ(9)-tetrahydrocannabinol, Δ(9)-tetrahydrocannabinolic acid and cannabidiol in MPP+ affected murine mesencephalic cultures. Phytomedicine. 2012;19(8-9):819-24.
Moldzio, R., Pacher, T., Krewenka, C., Kranner, B., Novak, J., Duvigneau, J. C., & Rausch, W. D. (2012). Effects of cannabinoids Δ(9)-tetrahydrocannabinol, Δ(9)-tetrahydrocannabinolic acid and cannabidiol in MPP+ affected murine mesencephalic cultures. Phytomedicine : International Journal of Phytotherapy and Phytopharmacology, 19(8-9), 819-24. https://doi.org/10.1016/j.phymed.2012.04.002
Moldzio R, et al. Effects of Cannabinoids Δ(9)-tetrahydrocannabinol, Δ(9)-tetrahydrocannabinolic Acid and Cannabidiol in MPP+ Affected Murine Mesencephalic Cultures. Phytomedicine. 2012 Jun 15;19(8-9):819-24. PubMed PMID: 22571976.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Effects of cannabinoids Δ(9)-tetrahydrocannabinol, Δ(9)-tetrahydrocannabinolic acid and cannabidiol in MPP+ affected murine mesencephalic cultures. AU - Moldzio,Rudolf, AU - Pacher,Thomas, AU - Krewenka,Christopher, AU - Kranner,Barbara, AU - Novak,Johannes, AU - Duvigneau,Johanna Catharina, AU - Rausch,Wolf-Dieter, Y1 - 2012/05/07/ PY - 2011/10/03/received PY - 2012/02/28/revised PY - 2012/04/11/accepted PY - 2012/5/11/entrez PY - 2012/5/11/pubmed PY - 2012/12/10/medline SP - 819 EP - 24 JF - Phytomedicine : international journal of phytotherapy and phytopharmacology JO - Phytomedicine VL - 19 IS - 8-9 N2 - Cannabinoids derived from Cannabis sativa demonstrate neuroprotective properties in various cellular and animal models. Mitochondrial impairment and consecutive oxidative stress appear to be major molecular mechanisms of neurodegeneration. Therefore we studied some major cannabinoids, i.e. delta-9-tetrahydrocannabinolic acid (THCA), delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD) in mice mesencephalic cultures for their protective capacities against 1-methyl-4-phenyl pyridinium (MPP(+)) toxicity. MPP(+) is an established model compound in the research of parkinsonism that acts as a complex I inhibitor of the mitochondrial respiratory chain, resulting in excessive radical formation and cell degeneration. MPP(+) (10 μM) was administered for 48 h at the 9th DIV with or without concomitant cannabinoid treatment at concentrations ranging from 0.01 to 10 μM. All cannabinoids exhibited in vitro antioxidative action ranging from 669 ± 11.1 (THC), 16 ± 3.2 (THCA) to 356 ± 29.5 (CBD) μg Trolox (a vitamin E derivative)/mg substance in the 1,1-diphenyl-2-picrylhydrazyl radical (DPPH) assay. Cannabinoids were without effect on the morphology of dopaminergic cells stained by tyrosine hydroxylase (TH) immunoreaction. THC caused a dose-dependent increase of cell count up to 17.3% at 10 μM, whereas CBD only had an effect at highest concentrations (decrease of cell count by 10.1-20% at concentrations of 0.01-10 μM). It influenced the viability of the TH immunoreactive neurons significantly, whereas THCA exerts no influence on dopaminergic cell count. Exposure of cultures to 10 μM of MPP(+) for 48 h significantly decreased the number of TH immunoreactive neurons by 44.7%, and shrunken cell bodies and reduced neurite lengths could be observed. Concomitant treatment of cultures with cannabinoids rescued dopaminergic cells. Compared to MPP(+) treated cultures, THC counteracted toxic effects in a dose-dependent manner. THCA and CBD treatment at a concentration of 10 μM lead to significantly increased cell counts to 123% and 117%, respectively. Even though no significant preservation or recovery of neurite outgrowth to control values could be observed, our data show that cannabinoids THC and THCA protect dopaminergic neurons against MPP(+) induced cell death. SN - 1618-095X UR - https://www.unboundmedicine.com/medline/citation/22571976/Effects_of_cannabinoids_Δ_9__tetrahydrocannabinol_Δ_9__tetrahydrocannabinolic_acid_and_cannabidiol_in_MPP+_affected_murine_mesencephalic_cultures_ DB - PRIME DP - Unbound Medicine ER -