TY - JOUR
T1 - URB597 Prevents the Short-Term Excitotoxic Cell Damage in Rat Cortical Slices
T2 - Role of Cannabinoid 1 Receptors
AU - Chavira-Ramos, Karla
AU - Orozco-Morales, Mario
AU - Karasu, Çimen
AU - Tinkov, Alexey A.
AU - Aschner, Michael
AU - Santamaría, Abel
AU - Colín-González, Ana Laura
N1 - Funding Information:
This work was supported by the CONACYT-TUBITAK collaborative agreement (grant 265991 given to AS) and the National Institute of Environmental Health Sciences (grants R01ES03771, R01ES10563, and R01ES020852 given to MA). None of the sponsors were involved in design, collection, analysis, or interpretation of data, neither in writing of the report or decision to submit the article for publication.
Publisher Copyright:
© 2020, Springer Science+Business Media, LLC, part of Springer Nature.
PY - 2021/4
Y1 - 2021/4
N2 - Endocannabinoid-based therapies constitute an emerging tool for the potential treatment of neurodegenerative disorders, requiring characterization at the experimental level. The effects of URB597, an inhibitor of the fatty acid amide hydrolase (FAAH), were tested against the quinolinic acid (QUIN)-induced early toxic effects in rat cortical slices, and compared with those effects exerted by the endocannabinoid anandamide (AEA). URB597 prevented the QUIN-induced loss of mitochondrial function/cell viability and lipid peroxidation, while reduced necrosis, and to a lesser extent, apoptosis. The protective effects of URB597 were mediated by activation of cannabinoid receptor 1 (CB1r), as evidenced by their inhibition by the selective CB1r antagonist AM281. Similar effects were observed when testing AEA against QUIN toxicity. Our findings demonstrate the neuroprotective properties of URB597 during the early stages of excitotoxic damage to cortical tissue, suggesting that these properties are mediated by FAAH inhibition, and might be linked to the protective effects of AEA, or the combination of endocannabinoids.
AB - Endocannabinoid-based therapies constitute an emerging tool for the potential treatment of neurodegenerative disorders, requiring characterization at the experimental level. The effects of URB597, an inhibitor of the fatty acid amide hydrolase (FAAH), were tested against the quinolinic acid (QUIN)-induced early toxic effects in rat cortical slices, and compared with those effects exerted by the endocannabinoid anandamide (AEA). URB597 prevented the QUIN-induced loss of mitochondrial function/cell viability and lipid peroxidation, while reduced necrosis, and to a lesser extent, apoptosis. The protective effects of URB597 were mediated by activation of cannabinoid receptor 1 (CB1r), as evidenced by their inhibition by the selective CB1r antagonist AM281. Similar effects were observed when testing AEA against QUIN toxicity. Our findings demonstrate the neuroprotective properties of URB597 during the early stages of excitotoxic damage to cortical tissue, suggesting that these properties are mediated by FAAH inhibition, and might be linked to the protective effects of AEA, or the combination of endocannabinoids.
KW - AM281
KW - Anandamide
KW - Endocannabinoid system
KW - Excitotoxicity
KW - Fatty acid amide hydrolase
KW - URB597
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UR - http://www.scopus.com/inward/citedby.url?scp=85094882532&partnerID=8YFLogxK
U2 - 10.1007/s12640-020-00301-1
DO - 10.1007/s12640-020-00301-1
M3 - Article
C2 - 33141426
AN - SCOPUS:85094882532
SN - 1029-8428
VL - 39
SP - 146
EP - 155
JO - Neurotoxicity Research
JF - Neurotoxicity Research
IS - 2
ER -