CB2 receptor in the CNS: From immune and neuronal modulation to behavior.

Despite low levels of cannabinoid receptor type 2 (CB2R) expression in the central nervous system in human and rodents, a growing body of evidence shows CB2R involvement in many processes at the behavioral level, through both immune and neuronal modulations. Recent in vitro and in vivo evidence have highlighted the complex role of CB2R under physiological and inflammatory conditions. Under neuroinflammatory states, its activation seems to protect the brain and its functions, making it a promising target in a wide range of neurological disorders. Here, we provide a complete and updated overview of CB2R function in the central nervous system of rodents, spanning from modulation of immune function in microglia but also in other cell types, to behavior and neuronal activity, in both physiological and neuroinflammatory contexts.

Update on the controversial identity of cells expressing cnr2 gene in the nervous system.

The function of cannabinoid receptor type 2 (CB2R), mainly expressed by leukocytes, has long been limited to its peripheral immunomodulatory role. However, the use of CB2R-specific ligands and the availability of CB2R-Knock Out mice revealed that it could play a functional role in the CNS not only under physiological but also under pathological conditions. A direct effect on the nervous system emerged when CB2R mRNA was detected in neural tissues. However, accurate mapping of CB2R protein expression in the nervous system is still lacking, partly because of the lack of specificity of antibodies available. This review examines the regions and cells of the nervous system where CB2R protein is most likely present by cross-referencing mRNA and protein data published to date. Of the many antibodies developed to target CB2R, only a few have partially passed specificity tests and detected CB2R in the CNS. Efforts must be continued to support the development of more specific and better validated antibodies in each of the species in which CB2R protein is sought or needs to be quantified.