4.4 Article

URB597 Prevents the Short-Term Excitotoxic Cell Damage in Rat Cortical Slices: Role of Cannabinoid 1 Receptors

期刊

NEUROTOXICITY RESEARCH
卷 39, 期 2, 页码 146-155

出版社

SPRINGER
DOI: 10.1007/s12640-020-00301-1

关键词

URB597; Fatty acid amide hydrolase; Excitotoxicity; Anandamide; Endocannabinoid system; AM281

资金

  1. CONACYT-TUBITAK [265991]
  2. National Institute of Environmental Health Sciences [R01ES03771, R01ES10563, R01ES020852]

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Endocannabinoid-based therapies show potential as a tool for treating neurodegenerative disorders, with experimental studies demonstrating the neuroprotective properties of the FAAH inhibitor URB597 in preventing early toxic effects induced by QUIN in rat cortical tissue. The protective effects of URB597 were found to be mediated by the activation of CB1 receptors and were similar to those observed with AEA, suggesting a potential link between FAAH inhibition and the protective effects of endocannabinoids.
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.

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