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

TitleMicroglial Cannabinoid Type 1 Receptor Regulates Brain Inflammation in a Sex-Specific Manner.
Publication TypeJournal Article
Year of Publication2021
AuteursDe Meij, J, Alfanek, Z, Morel, L, Decoeur, F, Leyrolle, Q, Picard, K, Carrier, M, Aubert, A, Sere, A, Lucas, C, Laforest, G, Helbling, J-C, Tremblay, M-È, Cota, D, Moisan, M-P, Marsicano, G, Layé, S, Nadjar, A
JournalCannabis Cannabinoid Res
Volume6
Issue6
Pagination488-507
Date Published2021 12
ISSN2378-8763
KeywordsAnimals, Cannabinoids, Encephalitis, Male, Mice, Microglia, Neuroinflammatory Diseases, Receptors, Cannabinoid
Abstract

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 studies, microglia, the main source of cytokines in pathological conditions, express the cannabinoid type 1 receptor (CB1R). We thus developed a conditional mouse model of CB1R deletion specifically in microglia, which was subjected to an immune challenge (peripheral lipopolysaccharide injection). Our results reveal that microglial CB1R differentially controls sickness behavior in males and females. 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.

DOI10.1089/can.2020.0170
Alternate JournalCannabis Cannabinoid Res
PubMed ID34591647
PubMed Central IDPMC8713265