Inhibitions of anandamide transport and FAAH synthesis decrease apoptosis and oxidative stress through inhibition of TRPV1 channel in an in vitro seizure model

Molecular and Cellular Biochemistry
M NazıroğluBilal Çiğ

Abstract

The expression level of TRPV1 is high in hippocampus which is a main epileptic area in the brain. In addition to the actions of capsaicin (CAP) and reactive oxygen species (ROS), the TRPV1 channel is activated in neurons by endogenous cannabinoid, anandamide (AEA). In the current study, we investigated the role of inhibitors of TRPV1 (capsazepine, CPZ), AEA transport (AM404), and FAAH (URB597) on the modulation of Ca2+ entry, apoptosis, and oxidative stress in in vitro seizure-induced rat hippocampus and human glioblastoma (DBTRG) cell line. The seizure was induced in the hippocampal and DBTRG neurons using in vitro 4-aminopyridine (4-AP) to trigger a seizure-like activity model. CPZ and AM404 were fully effective in reversing 4-AP-induced intracellular free Ca2+ concentration of the hippocampus and TRPV1 current density of DBTRG. However, AEA and CAP did not activate TRPV1 in the URB597-treated neurons. Hence, we observed TRPV1 blocker effects of URB597 in the DBTRG neurons. In addition, the AM404 and CPZ treatments decreased intracellular ROS production, mitochondrial membrane depolarization, apoptosis, caspases 3 and 9 values in the hippocampus. In conclusion, the results indicate that inhibition of AEA transport, FAAH synth...Continue Reading

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Citations

Aug 2, 2019·Current Neuropharmacology·Eric Murillo-RodríguezPablo Torterolo
Jan 11, 2020·Frontiers in Cellular Neuroscience·Soraya Wilke SalibaBernd L Fiebich
Nov 4, 2020·Neurotoxicity Research·Karla Chavira-RamosAna Laura Colín-González
Nov 19, 2020·International Journal of Molecular Sciences·Cecilia Zavala-TecuapetlaHiram Luna-Munguia
Jan 7, 2021·Journal of Receptor and Signal Transduction Research·Fatma Nihan CankaraCaner Günaydın
Nov 8, 2020·Neurochemistry International·Bao XueYing Wang
Jun 3, 2021·International Journal of Molecular Sciences·Rosa Maria VitalePietro Amodeo
Dec 17, 2019·Epilepsy & Behavior : E&B·Laila AsthFabrício A Moreira
Dec 7, 2021·Frontiers in Pharmacology·Matthias ApweilerBernd L Fiebich

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Methods Mentioned

BETA
mechanical dissociation

Software Mentioned

SPSS

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