Cannabinoid receptor type 2 expression in mouse brain: from mapping to regulation in microglia under inflammatory conditions [snRNA-seq]

Since its detection in the brain, the cannabinoid receptor type 2 (CB2) has been considered a promising therapeutic target for various neurological and psychiatric disorders. However, precise brain mapping of its expression is still lacking. Using magnetic cell sorting, calibrated RT-qPCR and single-nucleus RNAseq, we show that CB2 is expressed at a low level in all brain regions studied, mainly by few microglial cells, and by neurons in an even lower proportion. Upon lipopolysaccharide stimulation, modeling neuroinflammation in non-sterile conditions, we demonstrate that the inflammatory response is associated with a transient reduction in CB2 mRNA levels in brain tissue, particularly in microglial cells. This result, confirmed in the BV2 microglial cell line, contrasts with the positive correlation observed between CB2 mRNA levels and the inflammatory response upon stimulation by interferon-gamma, modeling neuroinflammation in sterile condition. Discrete brain CB2 expression might thus be up- or down-regulated depending on the inflammatory context. Overall design: Nuclei of postnatal day 10 mouse cortex were isolated and then selected using Fluorescence-activated nuclei sorting (FANS) based on high DAPI intensity for analysis using snRNA-seq. Nuclei were individually captured by the iX Chromium (10x Genomics) and libraries were prepared according to 10x Genomics protocol.