PMID- 30255158
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20201001
IS  - 2578-5125 (Print)
IS  - 2378-8763 (Electronic)
IS  - 2378-8763 (Linking)
VI  - 3
IP  - 1
DP  - 2018
TI  - Oleoylethanolamide and Palmitoylethanolamide Protect Cultured Cortical Neurons 
      Against Hypoxia.
PG  - 171-178
LID - 10.1089/can.2018.0013 [doi]
AB  - Introduction: Perinatal hypoxic-ischemic (HI) encephalopathy is defined as a 
      neurological syndrome where the newborn suffers from acute ischemia and hypoxia 
      during the perinatal period. New therapies are needed. The acylethanolamides, 
      oleoylethanolamide (OEA) and palmitoylethanolamide (PEA), possess neuroprotective 
      properties, and they could be effective against perinatal HI. These lipid 
      mediators act through peroxisome proliferator-activated receptors subtype alpha 
      (PPARalpha), or transient receptor potential vanilloid (TRPV), such as TRPV subtype 1 
      and 4. Materials and Methods: The objectives of this study were to discern: (1) 
      the neuroprotective role of OEA and PEA in parietotemporal cortical neurons of 
      newborn rats and mice subjected to hypoxia, and (2) the role of the receptors, 
      PPARalpha, TRPV1, and TRPV4, in neuroprotective effects. Cell culture of cortical 
      neurons and the lactate dehydrogenase assay was carried out. The role of 
      receptors was discerned by using selective antagonist and agonist ligands, as 
      well as knockout (KO) PPARalpha mice. Results: The findings indicate that OEA and PEA 
      exert neuroprotective effects on cultured cortical neurons subjected to a hypoxic 
      episode. These protective effects are not mediated by the receptors, PPARalpha, 
      TRPV1, or TRPV4, because neither PPARalpha KO mice nor receptor ligands significantly 
      modify OEA and PEA-induced effects. Blocking TRPV4 with RN1734 is neuroprotective 
      per se, and cotreatment with OEA and PEA is able to enhance neuroprotective 
      effects of the acylethanolamides. Since stimulating TRPV4 was devoid of effects 
      on OEA and PEA-induced protective effects, effects of RN1734 cotreatment seem to 
      be a consequence of additive actions. Conclusion: The lipid mediators, OEA and 
      PEA, exert neuroprotective effects on cultured cortical neurons subjected to 
      hypoxia. Coadministration of OEA or PEA, and the TRPV4 antagonist RN1734 is able 
      to enhance neuroprotective effects. These in vitro results could be of utility 
      for developing new therapeutic tools against perinatal HI.
FAU - Portavella, Manuel
AU  - Portavella M
AD  - Laboratory of Animal Behavior and Neuroscience, Department of Experimental 
      Psychology, Faculty of Psychology, Universidad de Sevilla, Seville, Spain.
FAU - Rodriguez-Espinosa, Nieves
AU  - Rodriguez-Espinosa N
AD  - Neurophysiology and Molecular Neurology Lab, Department of Medical Physiology and 
      Biophysics, Faculty of Medicine, Universidad de Sevilla, Seville, Spain.
FAU - Galeano, Pablo
AU  - Galeano P
AD  - Biochemical Research Institute of Buenos Aires (IIBBA-CONICET), Buenos Aires, 
      Argentina.
FAU - Blanco, Eduardo
AU  - Blanco E
AD  - University of Lleida, Medical Research Institute, Dr. Pifarre Foundation 
      (IRBLleida), Lleida, Spain.
FAU - Romero, Juan I
AU  - Romero JI
AD  - Biochemical Research Institute of Buenos Aires (IIBBA-CONICET), Buenos Aires, 
      Argentina.
FAU - Holubiec, Mariana I
AU  - Holubiec MI
AD  - Biochemical Research Institute of Buenos Aires (IIBBA-CONICET), Buenos Aires, 
      Argentina.
FAU - Rodriguez de Fonseca, Fernando
AU  - Rodriguez de Fonseca F
AD  - UGC Mental Health, Regional University Hospital of Malaga, Institute IBIMA, 
      Malaga, Spain.
FAU - Fernandez-Espejo, Emilio
AU  - Fernandez-Espejo E
AD  - Neurophysiology and Molecular Neurology Lab, Department of Medical Physiology and 
      Biophysics, Faculty of Medicine, Universidad de Sevilla, Seville, Spain.
LA  - eng
PT  - Journal Article
DEP - 20180919
PL  - United States
TA  - Cannabis Cannabinoid Res
JT  - Cannabis and cannabinoid research
JID - 101684827
PMC - PMC6148719
OTO - NOTNLM
OT  - PPARalpha
OT  - TRPV4
OT  - hypoxic-ischemic
OT  - neuroprotection
OT  - oleoylethanolamide
OT  - palmitoylethanolamide
COIS- The authors declare that there are no conflicts of interest.
EDAT- 2018/09/27 06:00
MHDA- 2018/09/27 06:01
PMCR- 2018/09/19
CRDT- 2018/09/27 06:00
PHST- 2018/09/27 06:00 [entrez]
PHST- 2018/09/27 06:00 [pubmed]
PHST- 2018/09/27 06:01 [medline]
PHST- 2018/09/19 00:00 [pmc-release]
AID - 10.1089/can.2018.0013 [pii]
AID - 10.1089/can.2018.0013 [doi]
PST - epublish
SO  - Cannabis Cannabinoid Res. 2018 Sep 19;3(1):171-178. doi: 10.1089/can.2018.0013. 
      eCollection 2018.