Proconvulsant effect of trans-cinnamaldehyde in pentylenetetrazole-induced kindling model of epilepsy: The role of TRPA1 channels

• Published in: Neuroscience letters 2020-03, Vol.721, p.134823, Article 134823
• Main Authors: Günaydın, Caner, Arslan, Gökhan, Bilge, S. Sırrı
• Format: Article
• Language: English
• Subjects: Acrolein - analogs & derivatives; Acrolein - toxicity; Animals; BDNF; Convulsants - toxicity; Dose-Response Relationship, Drug; Electrocorticography - drug effects; Electrocorticography - methods; Epilepsy - chemically induced; Epilepsy - metabolism; Kindling; Kindling, Neurologic - drug effects; Kindling, Neurologic - physiology; Male; NR2B; Pentylenetetrazole; Pentylenetetrazole - toxicity; Random Allocation; Rats; Rats, Sprague-Dawley; Transcinnamaldehyde; TRPA1 Cation Channel - metabolism; TRPA1 channels
• ISSN: 0304-3940; 1872-7972
• DOI: 10.1016/j.neulet.2020.134823

•Sub-chronic administration of TRPA1 agonist trans-cinnamaldehyde (TCA) causes a decrease in myoclonic jerk latency and increases seizure stage in PTZ-induced kindled rats.•Electrocorticographical (ECoG) recordings reveal that TCA increased the total spike number during 30 min after PTZ injection.•Administration of TCA for 14 consecutive days enhanced the expression levels of CREB, BDNF, and NR2B, which were increased by the repeated PTZ injections. The transient receptor potential ankyrin 1 (TRPA1), a member of the TRP superfamily, is widely distributed in the central nervous system (CNS) and plays an important role in pain and inflammation. However, no data has been reported regarding the effects of TRPA1 on epileptic seizures. Thus, this study was designed to investigate the sub-chronic effect of trans-cinnamaldehyde (TCA), an agonist of TRPA1, in pentylenetetrazole (PTZ) induced kindling model via electrocorticography (ECoG). Furthermore, the expressions of cAMP response element binding protein (CREB), brain-derived neurotrophic factor (BDNF), and NMDA receptor subunit NR2B were measured using Western blotting. Rats were kindled by intraperitoneal (i.p.) PTZ (35 mg/kg) injections. After electrode implantation and healing period, 10 and 30 mg/kg TCA was given i.p. for 14 consecutive days. On the next day, ECoG recordings were obtained after the injection of PTZ (35 mg/kg, i.p.), and twenty-four hours later, rats were decapitated for molecular analyses. TCA, at a dose of 30 mg/kg, decreased the first myoclonic jerk latency and increased seizure duration and total spike activity. Additionally, both doses of TCA enhanced CREB, BDNF, and NR2B expressions, which were increased by the kindling. The evidence from this study suggests that long term activation of TRPA1 channels causes an exacerbated seizure activity. Moreover, PTZ-induced increases in CREB, BDNF, and NR2B levels were enhanced by the repeated administrations of TCA.