PMID- 32824740
OWN - NLM
STAT- MEDLINE
DCOM- 20210614
LR  - 20210614
IS  - 2218-273X (Electronic)
IS  - 2218-273X (Linking)
VI  - 10
IP  - 8
DP  - 2020 Aug 18
TI  - CB2 Receptors and Neuron-Glia Interactions Modulate Neurotoxicity Generated by 
      MAGL Inhibition.
LID - 10.3390/biom10081198 [doi]
LID - 1198
AB  - 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.
FAU - Rojo-Bustamante, Estefania
AU  - Rojo-Bustamante E
AUID- ORCID: 0000-0003-3374-5458
AD  - Facultad de Ciencias, Departamento de Bioquimica y Genetica, Universidad de 
      Navarra, 31008 Pamplona, Spain.
FAU - Inigo-Marco, Ignacio
AU  - Inigo-Marco I
AD  - CIMA, Programa de Neurociencias, Universidad de Navarra, 31008 Pamplona, Spain.
FAU - Abellanas, Miguel Angel
AU  - Abellanas MA
AD  - Facultad de Ciencias, Departamento de Bioquimica y Genetica, Universidad de 
      Navarra, 31008 Pamplona, Spain.
FAU - Vinueza-Gavilanes, Rodrigo
AU  - Vinueza-Gavilanes R
AD  - CIMA, Programa de Neurociencias, Universidad de Navarra, 31008 Pamplona, Spain.
FAU - Baltanas, Ana
AU  - Baltanas A
AD  - CIMA, Programa de Neurociencias, Universidad de Navarra, 31008 Pamplona, Spain.
FAU - Luquin, Esther
AU  - Luquin E
AUID- ORCID: 0000-0002-9694-2953
AD  - Facultad de Medicina, Departamento de Patologia, Anatomia y Fisiologia, 
      Universidad de Navarra, 31008 Pamplona, Spain.
FAU - Arrasate, Montserrat
AU  - Arrasate M
AD  - CIMA, Programa de Neurociencias, Universidad de Navarra, 31008 Pamplona, Spain.
AD  - Facultad de Medicina, Departamento de Patologia, Anatomia y Fisiologia, 
      Universidad de Navarra, 31008 Pamplona, Spain.
AD  - IdiSNA, Instituto de Investigacion Sanitaria de Navarra, 31008 Pamplona, Spain.
FAU - Aymerich, Maria S
AU  - Aymerich MS
AD  - Facultad de Ciencias, Departamento de Bioquimica y Genetica, Universidad de 
      Navarra, 31008 Pamplona, Spain.
AD  - CIMA, Programa de Neurociencias, Universidad de Navarra, 31008 Pamplona, Spain.
AD  - IdiSNA, Instituto de Investigacion Sanitaria de Navarra, 31008 Pamplona, Spain.
LA  - eng
GR  - PI17/01931/Instituto de Salud Carlos III/International
GR  - BFU2017-90043-P/Ministerio de Ciencia, Innovacion y Universidades/International
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20200818
PL  - Switzerland
TA  - Biomolecules
JT  - Biomolecules
JID - 101596414
RN  - 0 (1,1,1,3,3,3-hexafluoropropan-2-yl 
      4-(bis(benzo(d)(1,3)dioxol-5-yl)(hydroxy)methyl)piperidine-1-carboxylate)
RN  - 0 (Benzodioxoles)
RN  - 0 (Cnr2 protein, rat)
RN  - 0 (Piperidines)
RN  - 0 (Receptor, Cannabinoid, CB2)
RN  - EC 3.1.1.23 (Monoacylglycerol Lipases)
SB  - IM
MH  - Animals
MH  - Benzodioxoles/*adverse effects
MH  - Cell Communication
MH  - Cell Survival/drug effects
MH  - Cells, Cultured
MH  - Coculture Techniques
MH  - Monoacylglycerol Lipases/antagonists & inhibitors
MH  - Neuroglia/*cytology/drug effects/metabolism
MH  - Neurons/*cytology/drug effects/metabolism
MH  - Piperidines/*adverse effects
MH  - Primary Cell Culture
MH  - Rats
MH  - Receptor, Cannabinoid, CB2/*metabolism
PMC - PMC7464766
OTO - NOTNLM
OT  - CB2 receptors
OT  - KML29
OT  - endocannabinoid system
OT  - microglia
OT  - monoacylglycerol lipase
OT  - neuroprotection
COIS- The authors declare no conflict of interest.
EDAT- 2020/08/23 06:00
MHDA- 2021/06/16 06:00
PMCR- 2020/08/01
CRDT- 2020/08/23 06:00
PHST- 2020/06/30 00:00 [received]
PHST- 2020/07/30 00:00 [revised]
PHST- 2020/08/12 00:00 [accepted]
PHST- 2020/08/23 06:00 [entrez]
PHST- 2020/08/23 06:00 [pubmed]
PHST- 2021/06/16 06:00 [medline]
PHST- 2020/08/01 00:00 [pmc-release]
AID - biom10081198 [pii]
AID - biomolecules-10-01198 [pii]
AID - 10.3390/biom10081198 [doi]
PST - epublish
SO  - Biomolecules. 2020 Aug 18;10(8):1198. doi: 10.3390/biom10081198.