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Published on: July 23, 2012
Cannabinoid receptors in microglia of the central nervous system: immune functional relevance
G A Cabral1, F Marciano-Cabral
1Department of Microbiology and Immunology, Virginia Commonwealth University, School of Medicine, 1101 E. Marshall Street, Richmond, VA 23298-0678, USA. gacabral@hsc.vcu.edu
Abstract:
Microglia, resident macrophages of the brain, function as immune effector and accessory cells. Paradoxically, they not only play a role in host defense and tissue repair but also have been implicated in a variety of neuropathological processes. Microglia, in addition to exhibiting phenotypic markers for macrophages, express CB1 and CB2 cannabinoid receptors. Recent studies suggest the existence of a third, yet-to-be cloned, non-CB1, non-CB2 cannabinoid receptor. These receptors appear to be functionally relevant within defined windows of microglial activation state and have been implicated as linked to cannabinoid modulation of chemokine and cytokine expression. The recognition that microglia express cannabinoid receptors and that their activation results in modulation of select cellular activities suggests that they may be amenable to therapeutic manipulation for ablating untoward inflammatory responses in the central nervous system.
Insights
Microglia, the brain's immune cells, express cannabinoid receptors. Targeting these receptors may offer new therapies for central nervous system inflammation.
Area of Science:
- Neuroimmunology
- Cellular Biology
- Pharmacology
Background:
- Microglia are the primary immune cells in the central nervous system (CNS).
- Microglia play dual roles in host defense, tissue repair, and neuropathology.
- Microglia express CB1 and CB2 cannabinoid receptors, with evidence suggesting a third receptor exists.
Purpose of the Study:
- To investigate the role of cannabinoid receptors on microglia.
- To explore the potential of targeting microglial cannabinoid receptors for therapeutic intervention in CNS disorders.
Main Methods:
- Phenotypic analysis of microglia.
- Investigation of cannabinoid receptor expression (CB1, CB2, and potential novel receptors).
- Assessment of cannabinoid modulation on microglial chemokine and cytokine expression.
Main Results:
- Microglia express functional cannabinoid receptors (CB1 and CB2).
- Evidence supports the existence of a novel, non-CB1, non-CB2 cannabinoid receptor on microglia.
- Cannabinoid receptor activation modulates microglial chemokine and cytokine profiles.
Conclusions:
- Microglia possess functionally relevant cannabinoid receptors.
- These receptors are linked to the modulation of inflammatory mediators in the CNS.
- Microglial cannabinoid receptors represent a potential therapeutic target for neuroinflammatory diseases.
