Abstract |
This study was aimed to investigate whether treatment with purified cannabidiol (CBD) may counteract the development of experimental multiple sclerosis (MS), by targeting the PI3K/Akt/mTOR pathway. Although the PI3K/Akt/mTOR pathway was found to be activated by cannabinoids in several immune and non-immune cells, currently, there is no data about the effects of CBD in the PI3K/Akt/mTOR activity in MS. Experimental Autoimmune Encephalomyelitis (EAE), the most common model of MS, was induced in C57BL/6 mice by immunization with myelin oligodendroglial glycoprotein peptide (MOG)35-55. After EAE onset, which occurs approximately 14days after disease induction, mice were daily intraperitoneally treated with CBD (10mg/kg mouse) and observed for clinical signs of EAE. At 28days from EAE-induction, mice were euthanized and spinal cord tissues were sampled to perform immunohistochemical evaluations and western blot analysis. Our results showed a clear downregulation of the PI3K/Akt/mTOR pathway following EAE induction. CBD treatment was able to restore it, increasing significantly the phosphorylation of PI3K, Akt and mTOR. Also, an increased level of BNDF in CBD-treated mice seems to be involved in the activation of PI3K/Akt/mTOR pathway. In addition, our data demonstrated that therapeutic efficacy of CBD treatment is due to reduction of pro-inflammatory cytokines, like IFN-γ and IL-17 together with an up-regulation of PPARγ. Finally, CBD was found to promote neuronal survival by inhibiting JNK and p38 MAP kinases. These results provide an interesting discovery about the regulation of the PI3K/Akt/mTOR pathway by cannabidiol administration, that could be a new potential therapeutic target for MS management.
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Authors | Sabrina Giacoppo, Federica Pollastro, Gianpaolo Grassi, Placido Bramanti, Emanuela Mazzon |
Journal | Fitoterapia
(Fitoterapia)
Vol. 116
Pg. 77-84
(Jan 2017)
ISSN: 1873-6971 [Electronic] Netherlands |
PMID | 27890794
(Publication Type: Journal Article)
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Copyright | Copyright © 2016 Elsevier B.V. All rights reserved. |
Chemical References |
- Brain-Derived Neurotrophic Factor
- Interleukin-17
- PPAR gamma
- Cannabidiol
- Interferon-gamma
- mTOR protein, mouse
- Proto-Oncogene Proteins c-akt
- TOR Serine-Threonine Kinases
- JNK Mitogen-Activated Protein Kinases
- p38 Mitogen-Activated Protein Kinases
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Topics |
- Animals
- Brain-Derived Neurotrophic Factor
(metabolism)
- Cannabidiol
(pharmacology)
- Encephalomyelitis, Autoimmune, Experimental
(drug therapy)
- Interferon-gamma
(metabolism)
- Interleukin-17
(metabolism)
- JNK Mitogen-Activated Protein Kinases
(metabolism)
- Male
- Mice
- Mice, Inbred C57BL
- PPAR gamma
(metabolism)
- Phosphatidylinositol 3-Kinases
(metabolism)
- Phosphorylation
- Proto-Oncogene Proteins c-akt
(metabolism)
- Signal Transduction
(drug effects)
- TOR Serine-Threonine Kinases
(metabolism)
- p38 Mitogen-Activated Protein Kinases
(metabolism)
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