Excitotoxicity in a chronic model of multiple sclerosis: Neuroprotective effects of cannabinoids through CB1 and CB2 receptor activation.
Inflammation, autoimmune response, demyelination and axonal damage are thought to participate in the pathogenesis of multiple sclerosis (MS). Understanding whether axonal damage causes or originates from demyelination is a crucial issue. Excitotoxic processes may be responsible for white matter and axonal damage. Experimental and clinical studies indicate that cannabinoids could prove efficient in the treatment of MS. Using a chronic model of MS in mice, we show here that clinical signs and axonal damage in the spinal cord were reduced by the AMPA antagonist, NBQX. Amelioration of symptomatology by the synthetic cannabinoid HU210 was also accompanied by a reduction of axonal damage in this model. Moreover, HU210 reduced AMPA-induced excitotoxicity both in vivo and in vitro through the obligatory activation of both CB1 and CB2 cannabinoid receptors. Together, these data underline the implication of excitotoxic processes in demyelinating pathologies such as MS and the potential therapeutic properties of cannabinoids.
Docagne
Fabian
F
Grupo de Neuroinmunología - Instituto Ramón y Cajal, CSIC -Avda Dr Arce, 37 - 28002 Madrid, Spain.
Muñetón
Vilma
V
Clemente
Diego
D
Ali
Carine
C
Loría
Frida
F
Correa
Fernando
F
Hernangómez
Míriam
M
Mestre
Leyre
L
Vivien
Denis
D
Guaza
Carmen
C
D000818:Animals; D015153:Blotting, Western; D002186:Cannabinoids / Q000627:therapeutic use*; D003711:Demyelinating Diseases / Q000473:pathology / Q000517:prevention & control; D004195:Disease Models, Animal; D004591:Electrophoresis, Polyacrylamide Gel; D018691:Excitatory Amino Acid Antagonists / Q000627:therapeutic use*; D005260:Female; D007150:Immunohistochemistry; D051379:Mice; D020528:Multiple Sclerosis, Chronic Progressive / Q000188:drug therapy* / Q000473:pathology; D018696:Neuroprotective Agents / Q000627:therapeutic use; D011810:Quinoxalines / Q000627:therapeutic use*; D043884:Receptor, Cannabinoid, CB1 / Q000187:drug effects / Q000378:metabolism*; D043885:Receptor, Cannabinoid, CB2 / Q000187:drug effects / Q000378:metabolism*; D013116:Spinal Cord / Q000187:drug effects / Q000473:pathology
D002186:Cannabinoids; D018691:Excitatory Amino Acid Antagonists; D018696:Neuroprotective Agents; D011810:Quinoxalines; D043884:Receptor, Cannabinoid, CB1; D043885:Receptor, Cannabinoid, CB2; C062865:2,3-dioxo-6-nitro-7-sulfamoylbenzo(f)quinoxaline