Cannabinoid CB1 receptor stimulation affords neuroprotection in MPTP-induced neurotoxicity by attenuating S100B up-regulation in vitro.
In this study, we investigated the mechanism of S100B neurotoxicity and the effect of cannabinoids, in C6 cells treated with 1-methyl-4-phenyl 1,2,3,6 tetrahydropyridine (MPTP) and co-cultured with differentiated PC12 cells. MPTP concentration- and time-dependently increased S100B density in C6 cells. This effect was followed by increased C6 cell proliferation and decreased cell viability of co-cultured PC12 cells. An antibody against S100B, given to PC12 cells before co-culture, led to their survival. Treatment with arachidonyl-2-chloroethylamide, a CB1 agonist, significantly inhibited MPTP-induced S100B density in C6 cells and protected co-cultured PC12 cells from cell death. Because MPTP selectively increased the levels of anandamide in C6 cells, the involvement of the endocannabinoid system was investigated by using selective inhibitors of endocannabinoid inactivation (cellular re-uptake or enzymatic hydrolysis) and selective cannabinoid CB1 and CB2 receptor antagonists and by silencing the CB1 receptor. Our data suggest that selective activation of CB1 receptors by either exogenous or endogenous cannabinoids might afford neuroprotection in MPTP-induced neurotoxicity also by controlling S100B up-regulation in activated glial cells.
Iuvone
Teresa
T
Department of Experimental Pharmacology, Faculty of Pharmacy, University of Naples Federico II, Via D. Montesano, 49, 80131, Naples, Italy, iuvone@unina.it
Esposito
Giuseppe
G
De Filippis
Daniele
D
Bisogno
Tiziana
T
Petrosino
Stefania
S
Scuderi
Caterina
C
Di Marzo
Vincenzo
V
Steardo
Luca
L
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / Q000009:adverse effects*; D000581:Amidohydrolases / Q000037:antagonists & inhibitors / Q000378:metabolism; D000818:Animals; D000906:Antibodies; D017209:Apoptosis / Q000187:drug effects; D001095:Arachidonic Acids / Q000378:metabolism / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism; D053148:Caspase 3 / Q000378:metabolism; D002450:Cell Communication / Q000187:drug effects; D002454:Cell Differentiation; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D018920:Coculture Techniques; D017077:Culture Media, Conditioned / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D063388:Endocannabinoids; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007211:Indoles / Q000494:pharmacology; D020267:MPTP Poisoning / Q000378:metabolism* / Q000473:pathology; D009414:Nerve Growth Factors / Q000276:immunology / Q000378:metabolism*; D009457:Neuroglia / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D009474:Neurons / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism / Q000473:pathology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D016716:PC12 Cells; D010880:Piperidines / Q000494:pharmacology; D053284:Polyunsaturated Alkamides / Q000378:metabolism; D011720:Pyrazoles / Q000494:pharmacology; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D051381:Rats; D043884:Receptor, Cannabinoid, CB1 / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D043885:Receptor, Cannabinoid, CB2 / Q000187:drug effects / Q000378:metabolism; D000077285:Rimonabant; D064568:S100 Calcium Binding Protein beta Subunit; D009418:S100 Proteins / Q000276:immunology / Q000378:metabolism*; D012701:Serotonin / Q000031:analogs & derivatives / Q000494:pharmacology; D013997:Time Factors; D015854:Up-Regulation; D000099252:Fatty Acid Amide Hydrolases
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D000581:Amidohydrolases; D000906:Antibodies; D001095:Arachidonic Acids; D002118:Calcium; D053148:Caspase 3; D017077:Culture Media, Conditioned; D063388:Endocannabinoids; D004791:Enzyme Inhibitors; D007211:Indoles; D009414:Nerve Growth Factors; D018696:Neuroprotective Agents; D010880:Piperidines; D053284:Polyunsaturated Alkamides; D011720:Pyrazoles; D034741:RNA, Small Interfering; D043884:Receptor, Cannabinoid, CB1; D043885:Receptor, Cannabinoid, CB2; D000077285:Rimonabant; D064568:S100 Calcium Binding Protein beta Subunit; D009418:S100 Proteins; D012701:Serotonin; D000099252:Fatty Acid Amide Hydrolases; C469526:Cnr2 protein, rat; C462953:N-(2-methyl-3-hydroxyphenyl)-5,8,11,14-eicosatetraenamide; C579158:S100b protein, rat; C114007:arachidonoylserotonin; C119325:arachidonyl-2-chloroethylamide; C505410:Casp3 protein, rat; C078814:anandamide; C402944:JHW 015