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CB2 Receptors and Neuron-Glia Interactions Modulate Neurotoxicity Generated by MAGL Inhibition.
- Source :
-
Biomolecules [Biomolecules] 2020 Aug 18; Vol. 10 (8). Date of Electronic Publication: 2020 Aug 18. - Publication Year :
- 2020
-
Abstract
- Monoacylglycerol lipase inhibition (MAGL) has emerged as an interesting therapeutic target for neurodegenerative disease treatment due to its ability to modulate the endocannabinoid system and to prevent the production of proinflammatory mediators. To obtain a beneficial response, it is necessary to understand how this inhibition affects the neuron-glia crosstalk and neuron viability. In this study, the effect of MAGL inhibition by KML29 was evaluated in two types of rat cortical primary cultures; mixed cultures, including neuron and glial cells, and neuron-enriched cultures. The risk of neuronal death was estimated by longitudinal survival analysis. The spontaneous neuronal risk of death in culture was higher in the absence of glial cells, a process that was enhanced by KML29 addition. In contrast, neuronal survival was not compromised by MAGL inhibition in the presence of glial cells. Blockade of cannabinoid type 2 (CB2) receptors expressed mainly by microglial cells did not affect the spontaneous neuronal death risk but decreased neuronal survival when KML29 was added. Modulation of cannabinoid type 1 (CB1) receptors did not affect neuronal survival. Our results show that neuron-glia interactions are essential for neuronal survival. CB2 receptors play a key role in these protective interactions when neurons are exposed to toxic conditions.
- Subjects :
- Animals
Cell Communication
Cell Survival drug effects
Cells, Cultured
Coculture Techniques
Monoacylglycerol Lipases antagonists & inhibitors
Neuroglia drug effects
Neuroglia metabolism
Neurons drug effects
Neurons metabolism
Primary Cell Culture
Rats
Benzodioxoles adverse effects
Neuroglia cytology
Neurons cytology
Piperidines adverse effects
Receptor, Cannabinoid, CB2 metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 2218-273X
- Volume :
- 10
- Issue :
- 8
- Database :
- MEDLINE
- Journal :
- Biomolecules
- Publication Type :
- Academic Journal
- Accession number :
- 32824740
- Full Text :
- https://doi.org/10.3390/biom10081198