Cannabinoid receptor type 2 expression in mouse brain: from mapping to regulation in microglia under inflammatory conditions

Since its detection in the brain, the cannabinoid receptor type 2 (CB2) has been deemed a promising therapeutic target for various neurological and psychiatric disorders. However, precise brain mapping of CB2 expression is currently lacking. Using magnetic cell sorting, calibrated reverse transcription-quantitative PCR, and single-nucleus RNA-seq, we revealed the low level of CB2 expression in all brain regions examined, mainly by a few microglial cells and by neurons in an even lower proportion. Upon lipopolysaccharide stimulation to simulate non-sterile neuroinflammatory conditions, we demonstrated that the inflammatory response was associated with a transient reduction in CB2 mRNA levels in the brain tissue, particularly in microglia. This result, confirmed in the BV2 microglial cells, contrasts with the positive correlation observed between CB2 mRNA levels and the inflammatory response upon stimulation by interferon-gamma, which models sterile inflammatory conditions. Thus, discrete brain CB2 expression may be upregulated or downregulated depending on the inflammatory context.