title: Neuroprotective properties of cannabigerol in Huntington's disease: studies in R6/2 mice and 3-nitropropionate-lesioned mice.
abstract: Different plant-derived and synthetic cannabinoids have shown to be neuroprotective in experimental models of Huntington's disease (HD) through cannabinoid receptor-dependent and/or independent mechanisms. Herein, we studied the effects of cannabigerol (CBG), a nonpsychotropic phytocannabinoid, in 2 different in vivo models of HD. CBG was extremely active as neuroprotectant in mice intoxicated with 3-nitropropionate (3NP), improving motor deficits and preserving striatal neurons against 3NP toxicity. In addition, CBG attenuated the reactive microgliosis and the upregulation of proinflammatory markers induced by 3NP, and improved the levels of antioxidant defenses that were also significantly reduced by 3NP. We also investigated the neuroprotective properties of CBG in R6/2 mice. Treatment with this phytocannabinoid produced a much lower, but significant, recovery in the deteriorated rotarod performance typical of R6/2 mice. Using HD array analysis, we were able to identify a series of genes linked to this disease (e.g., symplekin, Sin3a, Rcor1, histone deacetylase 2, huntingtin-associated protein 1, δ subunit of the gamma-aminobutyric acid-A receptor (GABA-A), and hippocalcin), whose expression was altered in R6/2 mice but partially normalized by CBG treatment. We also observed a modest improvement in the gene expression for brain-derived neurotrophic factor (BDNF), insulin-like growth factor-1 (IGF-1), and peroxisome proliferator-activated receptor-γ (PPARγ), which is altered in these mice, as well as a small, but significant, reduction in the aggregation of mutant huntingtin in the striatal parenchyma in CBG-treated animals. In conclusion, our results open new research avenues for the use of CBG, alone or in combination with other phytocannabinoids or therapies, for the treatment of neurodegenerative diseases such as HD.
authors.affiliation: Departamento de Bioquímica y Biología Molecular, Instituto Universitario de Investigación en Neuroquímica, Universidad Complutense, Madrid, 28040, Spain.
authors.forename: Sara
authors.initials: S
authors.lastname: Valdeolivas
authors.forename: Carmen
authors.initials: C
authors.lastname: Navarrete
authors.forename: Irene
authors.initials: I
authors.lastname: Cantarero
authors.forename: María L
authors.initials: ML
authors.lastname: Bellido
authors.forename: Eduardo
authors.initials: E
authors.lastname: Muñoz
authors.forename: Onintza
authors.initials: O
authors.lastname: Sagredo
mesh_terms: D000818:Animals; D001921:Brain / Q000187:drug effects*; D002186:Cannabinoids / Q000494:pharmacology*; D004195:Disease Models, Animal; D006816:Huntington Disease / Q000139:chemically induced / Q000473:pathology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018696:Neuroprotective Agents / Q000494:pharmacology*; D009574:Nitro Compounds / Q000633:toxicity; D011422:Propionates / Q000633:toxicity; D060888:Real-Time Polymerase Chain Reaction
chemical_list: D002186:Cannabinoids; D018696:Neuroprotective Agents; D009574:Nitro Compounds; D011422:Propionates; C037036:cannabigerol; C015392:3-nitropropionic acid