CB2 expression in mouse brain: from mapping to regulation in microglia under inflammatory conditions

Author:

Grabon Wanda1,Ruiz Anne2,Gasmi Nadia1,Degletagne Cyril3,Georges Béatrice1,Belmeguenai Amor1,Bodennec Jacques1,Rheims Sylvain1,Marcy Guillaume4,Bezin Laurent1

Affiliation:

1. Université Claude Bernard Lyon 1, CNRS UMR5292, Inserm U1028, Centre de Recherche en Neurosciences de Lyon, TIGER Team

2. Université Claude Bernard Lyon 1, CNRS UMR5292, Inserm U1028, Centre de Recherche en Neurosciences de Lyon, GenCyTi Platform

3. Cancer Genomic Platform, Centre Léon Bérard, Centre de Recherche en Cancérologie de Lyon, Université de Lyon, Université Claude Bernard Lyon 1, Inserm 1052, CNRS 5286

4. Université Claude Bernard Lyon 1, Bioinformatic Platform of the Labex Cortex

Abstract

Abstract 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.

Publisher

Research Square Platform LLC

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