Therapeutic action of cannabinoids in a murine model of multiple sclerosis.
Theiler's virus infection of the CNS induces an immune-mediated demyelinating disease in susceptible mouse strains and serves as a relevant infection model for human multiple sclerosis (MS). Cannabinoids may act as immunosuppressive compounds that have shown therapeutic potential in chronic inflammatory disorders. Using the Theiler's murine encephalomyelitis virus model, we report here that treatment with the synthetic cannabinoids WIN 55,212-2, ACEA, and JWH-015 during established disease significantly improved the neurological deficits in a long-lasting way. At a histological level, cannabinoids reduced microglial activation, abrogated major histocompatibility complex class II antigen expression, and decreased the number of CD4+ infiltrating T cells in the spinal cord. Both recovery of motor function and diminution of inflammation paralleled extensive remyelination. Overall, the data presented may have potential therapeutic implications in demyelinating pathologies such as MS; in particular, the possible involvement of cannabinoid receptor CB2 would enable nonpsychoactive therapy suitable for long-term use.
Arévalo-Martín
Angel
A
Neuroimmunology Group, Neural Plasticity Department, Cajal Institute, Consejo Superior de Investigaciones Científicas, 28002 Madrid, Spain.
Vela
José Miguel
JM
Molina-Holgado
Eduardo
E
Borrell
José
J
Guaza
Carmen
C
D000818:Animals; D001522:Behavior, Animal; D048588:Benzoxazines; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D002186:Cannabinoids / Q000627:therapeutic use*; D018188:Cardiovirus Infections / Q000175:diagnosis / Q000188:drug therapy* / Q000473:pathology; D002465:Cell Movement / Q000187:drug effects; D005260:Female; D007249:Inflammation / Q000188:drug therapy; D051379:Mice; D017628:Microglia / Q000166:cytology / Q000187:drug effects; D009025:Morpholines / Q000627:therapeutic use; D009048:Motor Skills; D009103:Multiple Sclerosis / Q000175:diagnosis / Q000188:drug therapy* / Q000821:virology; D009186:Myelin Sheath / Q000648:ultrastructure; D009281:Naphthalenes / Q000627:therapeutic use; D043882:Receptors, Cannabinoid; D011955:Receptors, Drug / Q000819:agonists; D013116:Spinal Cord / Q000276:immunology / Q000648:ultrastructure; D017945:Theilovirus
D048588:Benzoxazines; D002186:Cannabinoids; D009025:Morpholines; D009281:Naphthalenes; D043882:Receptors, Cannabinoid; D011955:Receptors, Drug; C070417:(3R)-((2,3-dihydro-5-methyl-3-((4-morpholinyl)methyl)pyrrolo-(1,2,3-de)-1,4-benzoxazin-6-yl)(1-naphthalenyl))methanone