The cannabinoid CP55,940 prolongs survival and improves locomotor activity in Drosophila melanogaster against paraquat: implications in Parkinson's disease.
Cannabinoids have been shown to function as protective agents via receptor-independent and/or receptor-dependent mechanisms against stressful conditions. However, the neuroprotective mechanism of cannabinoids is far from conclusive. Therefore, the genuine antioxidant impact of cannabinoids in vivo is still uncertain. In this study, we demonstrate for the first time that CP55,940, a nonselective CB(1)/CB(2) cannabinoid receptor agonist, significantly protects and rescues Drosophila melanogaster against paraquat (PQ) toxicity via a receptor-independent mechanism. Interestingly, CP55,940 restores the negative geotaxis activity (i.e., climbing capability) of the fly exposed to PQ. Moreover, Drosophila fed with (1-200 microM) SP600125, a specific inhibitor of the stress responsive Jun-N-terminal kinase (JNK) signaling, and 20 mM PQ increased survival percentage and movement function (i.e., climbing capability) when compared to flies only treated with PQ. Taken together our results suggest that exogenous antioxidant cannabinoids can protect against and rescue from locomotor dysfunction in wild type (Canton-S) Drosophila exposed to stress stimuli. Therefore, cannabinoids may offer promising avenues for the design of molecules to prevent, delay, or ameliorate the treatment of population at high risk of suffering Parkinson disease.
School of Medicine, Department of Internal Medicine, Neurosciences Research Program, University of Antioquia, Calle 62 # 52-59, Building 1, Room 412, SIU Medellin, Colombia. mdelrio@quimbaya.udea.edu.co
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M
Jimenez-Del-Rio
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A
Daza-Restrepo
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Velez-Pardo
D000818:Animals; D000873:Anthracenes / Q000008:administration & dosage; D000975:Antioxidants / Q000008:administration & dosage; D001522:Behavior, Animal / Q000187:drug effects; D003511:Cyclohexanols / Q000008:administration & dosage*; D004305:Dose-Response Relationship, Drug; D004331:Drosophila melanogaster; D004347:Drug Interactions; D004791:Enzyme Inhibitors / Q000008:administration & dosage; D005247:Feeding Behavior / Q000187:drug effects; D005260:Female; D005947:Glucose / Q000008:administration & dosage; D006540:Herbicides / Q000633:toxicity*; D007166:Immunosuppressive Agents / Q000008:administration & dosage*; D008297:Male; D009043:Motor Activity / Q000187:drug effects*; D010269:Paraquat / Q000633:toxicity*; D016019:Survival Analysis; D013997:Time Factors; D024505:Tocopherols / Q000008:administration & dosage
D000873:Anthracenes; D000975:Antioxidants; D003511:Cyclohexanols; D004791:Enzyme Inhibitors; D006540:Herbicides; D007166:Immunosuppressive Agents; C432165:pyrazolanthrone; C054649:3-(2-hydroxy-4-(1,1-dimethylheptyl)phenyl)-4-(3-hydroxypropyl)cyclohexanol; D005947:Glucose; D010269:Paraquat; D024505:Tocopherols