Microglial Cannabinoid Type 1 Receptor Regulates Brain Inflammation in a Sex-Specific Manner

Julia De Meij, Zain Alfanek, Lydie Morel, Fanny Decoeur, Quentin Leyrolle, Katherine Picard, Micael Carrier, Agnes Aubert, Alexandra Séré, Céline Lucas, Gerald Laforest, Jean-Christophe Helbling, Marie-Eve Tremblay, Daniela Cota, Marie-Pierre Moisan, Giovanni Marsicano, Sophie Layé, Agnès Nadjar
Cannabis and Cannabinoid Research. 2021-12-01; 6(6): 488-507
DOI: 10.1089/can.2020.0170

Read on PubMed

De Meij J(1), Alfanek Z(1), Morel L(1), Decoeur F(1), Leyrolle Q(1), Picard K(2)(3)(4), Carrier M(2)(3), Aubert A(1), Séré A(1), Lucas C(1), Laforest G(1), Helbling JC(1), Tremblay ME(2)(3)(4)(5)(6), Cota D(7), Moisan MP(1), Marsicano G(7), Layé S(1), Nadjar A(1)(7).

Author information:
(1)NutriNeuro, INRAE, Bordeaux INP, University of Bordeaux, Bordeaux, France.
(2)Axe Neurosciences, Centre de Recherche du CHU de Québec, Université Laval, Québec City, Canada.
(3)Division of Medical Sciences, University of Victoria, Victoria, Canada.
(4)Department of Molecular Medicine, Université Laval, Québec City, Canada.
(5)Neurology and Neurosurgery Department, McGill University, Montreal, Canada.
(6)Department of Biochemistry and Molecular Biology, The University of British Columbia, Vancouver, Canada.
(7)INSERM, Neurocentre Magendie, Physiopathologie de la Plasticité Neuronale, Bordeaux, France.

Background: Neuroinflammation is a key feature shared by most, if not all, neuropathologies. It involves complex biological processes that act as a protective mechanism to fight against the injurious stimuli, but it can lead to tissue damage if self-perpetuating. In this context, microglia, the main cellular actor of neuroinflammation in the brain, are seen as a double-edged sword. By phagocyting neuronal debris, these cells can not only provide tissue repair but can also contribute to neuronal damage by releasing harmful substances, including inflammatory cytokines. The mechanisms guiding these apparent opposing actions
are poorly known. The endocannabinoid system modulates the release of inflammatory factors such as cytokines and could represent a functional link between microglia and neuroinflammatory processes. According to transcriptomic databases and in vitro studies, microglia, the main source of cytokines in
pathological conditions, express the cannabinoid type 1 receptor (CB1R).

Methods: We thus developed a conditional mouse model of CB1R deletion specifically in microglia, which was subjected to an immune challenge (peripheral lipopolysaccharide injection).

Results: Our results reveal that microglial CB1R differentially controls sickness behavior in males and females.

Conclusion: These findings add to the comprehension of neuroinflammatory processes and might be of
great interest for future studies aimed at developing therapeutic strategies for brain disorders with higher prevalence in men.


Know more about