Related Experiment Video
Updated: Nov 3, 2025

Characterization and Isolation of Mouse Primary Microglia by Density Gradient Centrifugation
Published on: February 16, 2018
Microglial Adenosine Receptors: From Preconditioning to Modulating the M1/M2 Balance in Activated Cells
Rafael Franco1,2, Alejandro Lillo3, Rafael Rivas-Santisteban1,2
1CiberNed, Network Research Center, Neurodegenerative Diseases, Spanish National Health Institute Carlos III, 28034 Madrid, Spain.
Abstract:
Neuronal survival depends on the glia, that is, on the astroglial and microglial support. Neurons die and microglia are activated not only in neurodegenerative diseases but also in physiological aging. Activated microglia, once considered harmful, express two main phenotypes: the pro-inflammatory or M1, and the neuroprotective or M2. When neuroinflammation, i.e., microglial activation occurs, it is important to achieve a good M1/M2 balance, i.e., at some point M1 microglia must be skewed into M2 cells to impede chronic inflammation and to afford neuronal survival. G protein-coupled receptors in general and adenosine receptors in particular are potential targets for increasing the number of M2 cells. This article describes the mechanisms underlying microglial activation and analyzes whether these cells exposed to a first damaging event may be ready to be preconditioned to better react to exposure to more damaging events. Adenosine receptors are relevant due to their participation in preconditioning. They can also be overexpressed in activated microglial cells. The potential of adenosine receptors and complexes formed by adenosine receptors and cannabinoids as therapeutic targets to provide microglia-mediated neuroprotection is here discussed.
Insights
Microglia, crucial for neuronal survival, have M1 (pro-inflammatory) and M2 (neuroprotective) states. Targeting adenosine receptors may shift microglia to the M2 phenotype, aiding neuroprotection and combating neurodegeneration.
Area of Science:
- Neuroscience
- Immunology
- Cell Biology
Background:
- Neuronal survival is dependent on glial cells, including astrocytes and microglia.
- Microglial activation and neuronal death occur in both neurodegenerative diseases and normal aging.
- Activated microglia exhibit M1 (pro-inflammatory) and M2 (neuroprotective) phenotypes, necessitating a balance for neuronal health.
Purpose of the Study:
- To explore microglial activation mechanisms and their role in neuroprotection.
- To investigate the potential of preconditioning microglia to enhance responses to damaging events.
- To analyze adenosine receptors as therapeutic targets for modulating microglial phenotypes.
Main Methods:
- Review of mechanisms underlying microglial activation.
- Analysis of microglial responses to damaging events and preconditioning.
- Discussion of adenosine receptors and their complexes with cannabinoids as therapeutic targets.
Main Results:
- A balance between M1 and M2 microglial phenotypes is crucial for impeding chronic inflammation and ensuring neuronal survival.
- Adenosine receptors play a role in microglial preconditioning and can be overexpressed in activated microglia.
- Adenosine receptors and their complexes with cannabinoids show potential for microglia-mediated neuroprotection.
Conclusions:
- Modulating microglial phenotypes, particularly shifting towards the M2 state, is vital for neuroprotection.
- Adenosine receptors represent a promising therapeutic target for neurodegenerative conditions.
- Targeting adenosine receptors and cannabinoid complexes could offer novel strategies for microglia-mediated neuroprotection.
More Related Videos
Related Concept Videos
Cholinergic Receptors: Muscarinic
The subtypes M1, M3, and M5 couple with the Gq subunit and activate the phospholipase C (PLC) activity, mobilizing intracellular Ca2+....
Adrenergic Receptors: ɑ Subtype
Adrenaline ≥ Noradrenaline >> Isoprenaline
α-adrenoceptors are further divided into α1 and α2-adrenoceptors.
α1-Adrenoceptors: These receptors are located postsynaptically on the effector organs and cause constriction of smooth muscle mediated by activation of phospholipase...
GPCRs Regulate Adenylyl Cylase Activity

