Open AccessChanges in Endocannabinoid Receptors and Enzymes in the Spinal Cord of SOD 1 G93A Transgenic Mice and Evaluation of a Sativex ® ‐like Combination of Phytocannabinoids: Interest for Future Therapies in Amyotrophic Lateral Sclerosis
Author(s) -
MorenoMartet Miguel,
EspejoPorras Francisco,
FernándezRuiz Javier,
Lago Eva
Publication year - 2014
Publication title -
cns neuroscience and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.403
H-Index - 69
eISSN - 1755-5949
pISSN - 1755-5930
DOI - 10.1111/cns.12262
Subject(s) - endocannabinoid system , neuroprotection , pharmacology , cannabinoid receptor , cannabidiol , receptor , genetically modified mouse , 2 arachidonoylglycerol , cannabinoid , amyotrophic lateral sclerosis , chemistry , spinal cord , transgene , medicine , biochemistry , neuroscience , biology , cannabis , disease , psychiatry , gene , agonist
Summary Aims Cannabinoids afford neuroprotection in SOD 1 G93A mutant mice, an experimental model of amyotrophic lateral sclerosis ( ALS ). However, these mice have been poorly studied to identify alterations in those elements of the endocannabinoid system targeted by these treatments. Moreover, we studied the neuroprotective effect of the phytocannabinoid‐based medicine Sativex ® in these mice. Methods First, we analyzed the endocannabinoid receptors and enzymes in the spinal cord of SOD 1 G93A transgenic mice at a late stage of the disease. Second, 10‐week‐old transgenic mice were daily treated with an equimolecular combination of Δ 9 ‐tetrahydrocannabinol‐ and cannabidiol‐enriched botanical extracts (20 mg/kg for each phytocannabinoid). Results We found a significant increase of CB 2 receptors and NAPE ‐ PLD enzyme in SOD 1 G93A transgenic males and only CB 2 receptors in females. Pharmacological experiments demonstrated that the treatment of these mice with the Sativex ® ‐like combination of phytocannabinoids only produced weak improvements in the progression of neurological deficits and in the animal survival, particularly in females. Conclusions Our results demonstrated changes in endocannabinoid signaling, in particular a marked up‐regulation of CB 2 receptors, in SOD 1 G93A transgenic mice, and provide support that Sativex ® may serve as a novel disease‐modifying therapy in ALS .