The cannabinoid system and microglia in health and disease

Recent years have yielded significant advances in our understanding of microglia, the immune cells of the central nervous system (CNS). Microglia are key players in CNS development, immune surveillance, and the maintenance of proper neuronal function throughout life. In the healthy brain, homeostati...

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Veröffentlicht in:Neuropharmacology 2021-06, Vol.190, p.108555-108555, Article 108555
Hauptverfasser: Duffy, Samuel S., Hayes, Jessica P., Fiore, Nathan T., Moalem-Taylor, Gila
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Hayes, Jessica P.
Fiore, Nathan T.
Moalem-Taylor, Gila
description Recent years have yielded significant advances in our understanding of microglia, the immune cells of the central nervous system (CNS). Microglia are key players in CNS development, immune surveillance, and the maintenance of proper neuronal function throughout life. In the healthy brain, homeostatic microglia have a unique molecular signature. In neurological diseases, microglia become activated and adopt distinct transcriptomic signatures, including disease-associated microglia (DAM) implicated in neurodegenerative disorders. Homeostatic microglia synthesise the endogenous cannabinoids 2-arachidonoylglycerol and anandamide and express the cannabinoid receptors CB1 and CB2 at constitutively low levels. Upon activation, microglia significantly increase their synthesis of endocannabinoids and upregulate their expression of CB2 receptors, which promote a protective microglial phenotype by enhancing their production of neuroprotective factors and reducing their production of pro-inflammatory factors. Here, we summarise the effects of the microglial cannabinoid system in the CNS demyelinating disease multiple sclerosis, the neurodegenerative diseases Alzheimer's disease, Parkinson's disease and amyotrophic lateral sclerosis, chronic inflammatory and neuropathic pain, and psychiatric disorders including depression, anxiety and schizophrenia. We discuss the therapeutic potential of cannabinoids in regulating microglial activity and highlight the need to further investigate their specific microglia-dependent immunomodulatory effects. •Microglia express all components of the endocannabinoid system.•Cannabinoids promote the reparative state of microglia in MS.•Conflicting reports regarding microglia CB signalling in neurodegenerative diseases.•Cannabinoids promote neuroprotective microglia in pain and psychiatric disorders.•Further studies to elucidate microglial modulation by cannabinoids are necessary.
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subjects Alzheimer Disease - metabolism
Amyotrophic Lateral Sclerosis - metabolism
Anxiety Disorders - metabolism
Arachidonic Acids - metabolism
Cannabinoids
Chronic pain
Chronic Pain - metabolism
Demyelinating diseases
Depressive Disorder - metabolism
Endocannabinoids - metabolism
Endocannabinoids - physiology
Glycerides - metabolism
Humans
Mental Disorders - metabolism
Microglia
Microglia - metabolism
Microglia - physiology
Multiple Sclerosis - metabolism
Neuralgia - metabolism
Neurodegenerative diseases
Neurodegenerative Diseases - metabolism
Parkinson Disease - metabolism
Polyunsaturated Alkamides - metabolism
Psychiatric disorders
Receptor, Cannabinoid, CB1 - metabolism
Receptor, Cannabinoid, CB2 - metabolism
Schizophrenia - metabolism
title The cannabinoid system and microglia in health and disease
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