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

Chavira-Ramos K., Orozco-Morales M., KARASU Ç., Tinkov A. A., Aschner M., Santamaria A., ...Daha Fazla

NEUROTOXICITY RESEARCH, cilt.39, sa.2, ss.146-155, 2021 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 39 Sayı: 2
  • Basım Tarihi: 2021
  • Doi Numarası: 10.1007/s12640-020-00301-1
  • Dergi Adı: NEUROTOXICITY RESEARCH
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, EMBASE, MEDLINE
  • Sayfa Sayıları: ss.146-155
  • Anahtar Kelimeler: URB597, Fatty acid amide hydrolase, Excitotoxicity, Anandamide, Endocannabinoid system, AM281, ACID AMIDE HYDROLASE, ENDOCANNABINOID SYSTEM, BRAIN, FAAH, INHIBITION, PAIN
  • Gazi Üniversitesi Adresli: Evet

Özet

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.