Cannabinoid CB1 and CB2 Receptors and Fatty Acid Amide Hydrolase Are Specific Markers of Plaque Cell Subtypes in Human Multiple Sclerosis
Journal - Journal of Neuroscience
Increasing evidence supports the idea of a beneficial effectof cannabinoid compounds for the treatment of multiple sclerosis(MS). However, most experimental data come from animal modelsof MS. We investigated the status of cannabinoid CB1 and CB2receptors and fatty acid amide hydrolase (FAAH) enzyme in braintissue samples obtained from MS patients. Areas of demyelinationwere identified and classified as active, chronic, and inactiveplaques. CB1 and CB2 receptors and FAAH densities and cellularsites of expression were examined using immunohistochemistryand immunofluorescence. In MS samples, cannabinoid CB1 receptorswere expressed by cortical neurons, oligodendrocytes, and alsooligodendrocyte precursor cells, demonstrated using double immunofluorescencewith antibodies against the CB1 receptor with antibodies againsttype 2 microtubule-associated protein, myelin basic protein,and the platelet-derived growth factor receptor-, respectively.CB1 receptors were also present in macrophages and infiltratedT-lymphocytes. Conversely, CB2 receptors were present in T-lymphocytes,astrocytes, and perivascular and reactive microglia (major histocompatibilitycomplex class-II positive) in MS plaques. Specifically, CB2-positivemicroglial cells were evenly distributed within active plaquesbut 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 glialexpression of cannabinoid CB1 and CB2 receptors and FAAH enzymeis induced in MS, thus supporting a role for the endocannabinoidsystem in the pathogenesis and/or evolution of this disease.
|Keywords : ||cannabinoid receptors • multiple sclerosis • immunohistochemistry • neuroinflammation • FAAH • glia|