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CB2 Receptors and Neuron–Glia Interactions Modulate Neurotoxicity Generated by MAGL Inhibition
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...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7464766/ https://www.ncbi.nlm.nih.gov/pubmed/32824740 http://dx.doi.org/10.3390/biom10081198 |
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author | Rojo-Bustamante, Estefania Íñigo-Marco, Ignacio Abellanas, Miguel Angel Vinueza-Gavilanes, Rodrigo Baltanás, Ana Luquin, Esther Arrasate, Montserrat Aymerich, Maria S. |
author_facet | Rojo-Bustamante, Estefania Íñigo-Marco, Ignacio Abellanas, Miguel Angel Vinueza-Gavilanes, Rodrigo Baltanás, Ana Luquin, Esther Arrasate, Montserrat Aymerich, Maria S. |
author_sort | Rojo-Bustamante, Estefania |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-7464766 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-74647662020-09-04 CB2 Receptors and Neuron–Glia Interactions Modulate Neurotoxicity Generated by MAGL Inhibition Rojo-Bustamante, Estefania Íñigo-Marco, Ignacio Abellanas, Miguel Angel Vinueza-Gavilanes, Rodrigo Baltanás, Ana Luquin, Esther Arrasate, Montserrat Aymerich, Maria S. Biomolecules Article 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. MDPI 2020-08-18 /pmc/articles/PMC7464766/ /pubmed/32824740 http://dx.doi.org/10.3390/biom10081198 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Rojo-Bustamante, Estefania Íñigo-Marco, Ignacio Abellanas, Miguel Angel Vinueza-Gavilanes, Rodrigo Baltanás, Ana Luquin, Esther Arrasate, Montserrat Aymerich, Maria S. CB2 Receptors and Neuron–Glia Interactions Modulate Neurotoxicity Generated by MAGL Inhibition |
title | CB2 Receptors and Neuron–Glia Interactions Modulate Neurotoxicity Generated by MAGL Inhibition |
title_full | CB2 Receptors and Neuron–Glia Interactions Modulate Neurotoxicity Generated by MAGL Inhibition |
title_fullStr | CB2 Receptors and Neuron–Glia Interactions Modulate Neurotoxicity Generated by MAGL Inhibition |
title_full_unstemmed | CB2 Receptors and Neuron–Glia Interactions Modulate Neurotoxicity Generated by MAGL Inhibition |
title_short | CB2 Receptors and Neuron–Glia Interactions Modulate Neurotoxicity Generated by MAGL Inhibition |
title_sort | cb2 receptors and neuron–glia interactions modulate neurotoxicity generated by magl inhibition |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7464766/ https://www.ncbi.nlm.nih.gov/pubmed/32824740 http://dx.doi.org/10.3390/biom10081198 |
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