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...

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Bibliographic Details
Published in:Molecular and cellular neuroscience 2007-04, Vol.34 (4), p.551-561
Main Authors: Docagne, Fabian, Muñetón, Vilma, Clemente, Diego, Ali, Carine, Loría, Frida, Correa, Fernando, Hernangómez, Míriam, Mestre, Leyre, Vivien, Denis, Guaza, Carmen
Format: Article
Language:English
Subjects:
Animals
Axonal damage
Blotting, Western
Cannabinoids
Cannabinoids - therapeutic use
Demyelinating Diseases - pathology
Demyelinating Diseases - prevention & control
Disease Models, Animal
Electrophoresis, Polyacrylamide Gel
Excitatory Amino Acid Antagonists - therapeutic use
Excitotoxicity
Female
Immunohistochemistry
Mice
Multiple sclerosis
Multiple Sclerosis, Chronic Progressive - drug therapy
Multiple Sclerosis, Chronic Progressive - pathology
Neuroprotective Agents - therapeutic use
Quinoxalines - therapeutic use
Receptor, Cannabinoid, CB1 - drug effects
Receptor, Cannabinoid, CB1 - metabolism
Receptor, Cannabinoid, CB2 - drug effects
Receptor, Cannabinoid, CB2 - metabolism
Spinal Cord - drug effects
Spinal Cord - pathology
TMEV
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Summary: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.
ISSN:1044-7431
1095-9327
DOI:10.1016/j.mcn.2006.12.005