Abstract
Microglia are key to maintaining the homeostasis of the brain. These immune cells of the brain can be our biggest ally in fighting infections, but can worsen pathology or hinder recovery when uncontrolled. Thus, understanding how microglia contribute to neuroinflammatory processes and how their activity can be controlled is of great importance. It is known that activation of endocannabinoid system, and especially the cannabinoid type 2 receptor (CB2R), decreases inflammation. Alongside its non-psychoactive effect, it makes the CB2R receptor a perfect target for treating diseases accompanied by neuroinflammation including neurodegenerative diseases. However, the exact mechanisms by which CB2R regulates microglial activity are not yet understood. Here, we review the current knowledge on the roles of microglial CB2R from in vitro and in vivo studies. We look into CB2R function under physiological and pathological conditions and focus on four different disease models representing chronic and acute inflammation. We highlight open questions and controversies and provide an update on the latest discoveries that were enabled by the development of novel technologies. Also, we discuss the recent findings on the role of microglia CB2R in cognition and its role in neuron–microglia communication.
Highlights
Microglia represent a powerful tool that our brain uses to maintain homeostasis
CB2-green fluorescence protein (GFP) BAC transgenic mice revealed microglial cannabinoid type 2 receptor (CB2R) expression in healthy brain tissue [44], while CB2EGFP/f/f showed no expression of CB2Rs under physiological conditions, but an upregulation in microglia in response to inflammation accompanying Alzheimer’s disease (AD) [43]
We are not aware of any studies that directly investigated CB2R-mediated neuron–microglia interaction, but we have previously shown that CB1Rs on GABAergic neurons play a role in neuron–microglia communication via fractalkine/CX3CR1 [153]
Summary
Microglia represent a powerful tool that our brain uses to maintain homeostasis. They take care of the debris and dead cells, and actively fight against an assault. When the fight is over, they switch off their offensive behaviour and help in the healing process Due to their destructive potential it is crucial to maintain control over their actions, but up to date this goal of keeping the balance is still elusive. 2 (CB2R), might be the key to the underlying control mechanism, as this receptor plays a main role in regulating the switch between the pro- and anti-inflammatory phenotype of microglia. This could be a crucial step in developing therapies to treat diseases accompanied by neuroinflammation including neurodegenerative diseases.
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