Effects of cannabinoids Delta (9)-tetrahydrocannabinol, Delta (9)-tetrahydrocannabinolic acid and cannabidiol in MPP super(+) affected murine mesencephalic cultures

• Published in: Phytomedicine (Stuttgart) Vol. 19; no. 8-9; pp. 819 - 824
• Main Authors: Moldzio, Rudolf, Pacher, Thomas, Krewenka, Christopher, Kranner, Barbara, Novak, Johannes, Duvigneau, Johanna Catharina, Rausch, Wolf-Dieter
• Format: Journal Article
• Language: English
• Published: 15.06.2012
• Subjects: Cannabis sativa
• ISSN: 0944-7113
• DOI: 10.1016/j.phymed.2012.04.002

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 super(+)) toxicity. MPP super(+) 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 mu M) was administered for 48 h at the 9th DIV with or without concomitant cannabinoid treatment at concentrations ranging from 0.01 to 10 mu M. All cannabinoids exhibited in vitro antioxidative action ranging from 669 plus or minus 11.1 (THC), 16 plus or minus 3.2 (THCA) to 356 plus or minus 29.5 (CBD) mu g 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 mu M, whereas CBD only had an effect at highest concentrations (decrease of cell count by 10.1-20% at concentrations of 0.01-10 mu M). It influenced the viability of the TH immunoreactive neurons significantly, whereas THCA exerts no influence on dopaminergic cell count. Exposure of cultures to 10 mu M of MPP super(+) 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 super(+) treated cultures, THC counteracted toxic effects in a dose-dependent manner. THCA and CBD treatment at a concentration of 10 mu M 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 upsilon + induced cell death.