Article

Cannabinoid CB1 and CB2 Receptors and Fatty Acid Amide Hydrolase Are Specific Markers of Plaque Cell Subtypes in Human Multiple Sclerosis

Department of Pharmacology and Toxicology , Medical College of Wisconsin, Milwaukee, Wisconsin, United States
The Journal of Neuroscience : The Official Journal of the Society for Neuroscience (Impact Factor: 6.34). 03/2007; 27(9):2396-402. DOI: 10.1523/JNEUROSCI.4814-06.2007
Source: PubMed

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.

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    • "Interest has been renewed in the histopathology of MS plaques in recent years. MS plaques can be subdivided into different histopathological subtypes according to features such as their myeloid cell distribution, especially HLA-DR + -macrophages (Trapp et al., 1999; Chang et al., 2002; Frohman et al., 2006; Benito et al., 2007; Koning et al., 2007; Breij et al., 2008; Chang et al., 2008; Young et al., 2008; Clemente et al., 2011). Initially, active plaques exhibit abundant and evenly distributed HLA-DR + -cells (mostly large, round, lipid-laden macrophages), although when phagocytotic macrophages contain myelin protein debris the plaques are considered to be more recently formed. "
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    • "This effect was also observed when the endogenous levels of the eCB AEA are elevated by pharmacological intervention [161-163]. Microglial cells are possible targets for immunomodulatory activities of eCBs, a hypothesis that is supported by the presence of cannabinoid receptors and the enzymes responsible for their synthesis and degradation [122] [164] [165] [166]. The endogenous ligands AEA and 2-AG are also synthesized by microglial cells which produce approximately 20-fold more eCBs than neurons and astrocytes [166]. "
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    • "Scientific researchers have demonstrated that activation of both CB1 and CB2 receptors reduces the intensity of deficits such as spasticity, tremor or neuropathic pain; CB2 receptors activation, in addition, regulates the disease progression connected with the inflammatory process (20). "
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