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Cited by 143Cannabis and Cannabinoid ResearchGenetic Neurodegenerative DiseasesParkinson's Disease Mechanisms and Treatments

Neuroprotective properties of cannabigerol in Huntington's disease: studies in R6/2 mice and 3-nitropropionate-lesioned mice

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Valdeolivas, Sara, Navarrete, Carmen, Cantarero, Irene, Bellido, María L., Muñoz, Eduardo, Sagredo, Onintza·2015·Neurotherapeutics
DOI 10.1007/s13311-014-0304-zPMC PMC4322067
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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.

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  • In 3NP-treated mouse models, SGK1 expression levels rose 2.7-fold compared to controls, but treatment with cannabigerol resulted in a 1.41-fold decrease in SGK1 expression.

    “In 3NP-treated mouse models, SGK1 expression levels rose 2.7-fold compared to controls, but treatment with cannabigerol resulted in a 1.41-fold decrease in SGK1 expression”

    From Serum/glucocorticoid regulated kinase 1 (SGK1) in neurological disorders: pain or gain (2024) · cites this paper as Valdeolivas et al., 2015

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Authors
Valdeolivas, S., Navarrete, C., Cantarero, I., Bellido, M. L., Muñoz, E., & Sagredo, O.
Affiliations
  • Universidad Complutense de Madrid (ES)
  • Viva Biotech (China) (CN)
  • Instituto Maimónides de Investigación Biomédica de Córdoba (ES)
Corresponding author
Sagredo, Onintza
ORCID
Venue
Neurotherapeutics
Publisher
Elsevier BV
Published
2015-01
Volume
12
Issue
1
Pages
185-199
ISSN
1878-7479 (ISSN-L)
DOI
10.1007/s13311-014-0304-z
PMC
PMC4322067
OpenAlex
W2064204556
Cited by
143
References
1
Citations by year
2026: 14 · 2025: 13 · 2024: 12 · 2023: 16 · 2022: 15 · 2021: 17 · 2020: 15 · 2019: 10 · 2018: 7 · 2017: 11 · 2016: 8 · 2015: 3 · 2014: 1
FWCI
5.59
Type
journal article
Language
en
Open access
Licence
Locations
  • Neurotherapeutics (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • Ministerio de Ciencia e Innovación (CB06/05/0089, SAF2009/11847)
  • Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CB06/05/0089)
Topics
  • Health Sciences › Medicine › Pharmacology › Cannabis and Cannabinoid Research
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Genetic Neurodegenerative Diseases
  • Health Sciences › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
Keywords
cannabigerol, Huntington's disease, neuroprotection, phytocannabinoids, 3-nitropropionic acid, R6/2 mice, striatal neurons, microglial activation, neuroinflammation, oxidative stress, mutant huntingtin aggregation, gene expression profiling, brain-derived neurotrophic factor, insulin-like growth factor I, PPARγ, motor impairment
MeSH terms
Animals, Brain, Cannabinoids, Disease Models, Animal, Huntington Disease, Male, Mice, Inbred C57BL, Nitro Compounds, Propionates, Neuroprotective Agents, Mice, Real-Time Polymerase Chain Reaction

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