title: Cannabinoid CB1 and CB2 receptors and fatty acid amide hydrolase are specific markers of plaque cell subtypes in human multiple sclerosis.
abstract: Increasing evidence supports the idea of a beneficial effect of cannabinoid compounds for the treatment of multiple sclerosis (MS). However, most experimental data come from animal models of MS. We investigated the status of cannabinoid CB1 and CB2 receptors and fatty acid amide hydrolase (FAAH) enzyme in brain tissue samples obtained from MS patients. Areas of demyelination were identified and classified as active, chronic, and inactive plaques. CB1 and CB2 receptors and FAAH densities and cellular sites of expression were examined using immunohistochemistry and immunofluorescence. In MS samples, cannabinoid CB1 receptors were expressed by cortical neurons, oligodendrocytes, and also oligodendrocyte precursor cells, demonstrated using double immunofluorescence with antibodies against the CB1 receptor with antibodies against type 2 microtubule-associated protein, myelin basic protein, and the platelet-derived growth factor receptor-alpha, respectively. CB1 receptors were also present in macrophages and infiltrated T-lymphocytes. Conversely, CB2 receptors were present in T-lymphocytes, astrocytes, and perivascular and reactive microglia (major histocompatibility complex class-II positive) in MS plaques. Specifically, CB2-positive microglial cells were evenly distributed within active plaques but were located in the periphery of chronic active plaques. FAAH expression was restricted to neurons and hypertrophic astrocytes. As seen for other neuroinflammatory conditions, selective glial expression of cannabinoid CB1 and CB2 receptors and FAAH enzyme is induced in MS, thus supporting a role for the endocannabinoid system in the pathogenesis and/or evolution of this disease.
authors.affiliation: Laboratorio de Apoyo a la Investigación, Fundación Hospital Alcorcón, 28922 Madrid, Spain.
authors.forename: Cristina
authors.initials: C
authors.lastname: Benito
authors.forename: Juan Pablo
authors.initials: JP
authors.lastname: Romero
authors.forename: Rosa María
authors.initials: RM
authors.lastname: Tolón
authors.forename: Diego
authors.initials: D
authors.lastname: Clemente
authors.forename: Fabián
authors.initials: F
authors.lastname: Docagne
authors.forename: Cecilia J
authors.initials: CJ
authors.lastname: Hillard
authors.forename: Camen
authors.initials: C
authors.lastname: Guaza
authors.forename: Julián
authors.initials: J
authors.lastname: Romero
mesh_terms: D000368:Aged; D000581:Amidohydrolases / Q000378:metabolism*; D005455:Fluorescent Antibody Technique; D006801:Humans; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000378:metabolism* / Q000473:pathology*; D009457:Neuroglia / Q000378:metabolism; D043884:Receptor, Cannabinoid, CB1 / Q000378:metabolism*; D043885:Receptor, Cannabinoid, CB2 / Q000378:metabolism*; D013116:Spinal Cord / Q000378:metabolism / Q000473:pathology; D014018:Tissue Distribution; D000099252:Fatty Acid Amide Hydrolases
chemical_list: D000581:Amidohydrolases; D043884:Receptor, Cannabinoid, CB1; D043885:Receptor, Cannabinoid, CB2; D000099252:Fatty Acid Amide Hydrolases