Endocannabinoid signaling in microglia

Abstract

Microglia, the innate immune cells of the central nervous system (CNS), execute their sentinel, housekeeping and defense functions through a panoply of genes, receptors and released cytokines, chemokines and neurotrophic factors. Moreover, microglia functions are closely linked to the constant communication with other cell types, among them neurons. Depending on the signaling pathway and type of stimuli involved, the outcome of microglia operation can be neuroprotective or neurodegenerative. Accordingly, microglia are increasingly becoming considered cellular targets for therapeutic intervention. Among signals controlling microglia activity, the endocannabinoid (EC) system has been shown to exert a neuroprotective role in many neurological diseases. Like neurons, microglia express functional EC receptors and can produce and degrade ECs. Interestingly, boosting EC signaling leads to an antiinflammatory and neuroprotective microglia phenotype. Nonetheless, little evidence is available on the microglia-mediated therapeutic effects of EC compounds. This review focuses on the EC signals acting on the CNS microglia in physiological and pathological conditions, namely on the CB1R, CB2R and TRPV1-mediated regulation of microglia properties. It also provides new evidence, which strengthens the understanding of mechanisms underlying the control of microglia functions by ECs. Given the broad expression of the EC system in glial and neuronal cells, the resulting picture is the need for in vivo studies in transgenic mouse models to dissect the contribution of EC microglia signaling in the neuroprotective effects of EC-derived compounds.

Type‐1 cannabinoid receptors and their ever‐expanding roles in brain energy processes

“…CB 1 receptors are widely expressed across the brain parenchyma (Kano et al, 2009). A similar observation holds true when searching for the cell types that express CB 1 receptors in brain tissue, because not only neurons and astrocytes express this GPCR, but also other glia cells as oligodendrocytes and microglia (Marinelli et al, 2023;Molina-Holgado et al, 2023), whose activity exert an important role in brain physiology and pathophysiology (Parpura et al, 2012).…”

Jedi-1/MEGF12-mediated phagocytosis controls the pro-neurogenic properties of microglia in the ventricular-subventricular zone

“…Because endocannabinoids have also been implicated in regulating inflammatory pathways in microglia 42 , we measured the levels of several endocannabinoids/endocannabinoid-related lipids (2-arachidonoylglycerol (2-AG), oleoylglycerol (OG), and oleoylethanolamide (OEA)) as well as their precursor, arachidonic acid (AA). We found no significant differences in the concentration of AA, 2-AG, or OG between the two genotypes (data not shown), but OEA was significantly elevated in JKO V-SVZ relative to WT tissue (effect size ±SEM: 4.160 ± 1.605; 95% CI: 0.4585 to 7.862; p= 0.032).…”

β-arrestin1 regulates astrocytic reactivity via Drp1-dependent mitochondrial fission: implications in postoperative delirium

“…As microglia and astrocytes are the active players of brain inflammatory events and mediates the release of neurotrophic factors [ 30 ], we, therefore, used immunohistochemical method to detect the activated states of microglia and astrocytes in hippocampal tissues. After surgery, activation of microglia and astrocytes, manifested as increased numbers and enlarged areas in the immunohistochemical staining of glial fibrillary acidic protein (GFAP) and ionized calcium-binding adapter molecule 1 (Iba-1), were shown in dentate gyrus (DG) of mice (Fig.…”