Department of Pharmacology, School of Medicine, Ondokuz Mayis University, Samsun, Turkey.
Department of Physiology, School of Medicine, Ondokuz Mayis University, Samsun, Turkey.
Neurosci Lett. 2020 Mar 16;721:134823. doi: 10.1016/j.neulet.2020.134823. Epub 2020 Feb 5.
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.
瞬时受体电位锚蛋白 1（TRPA1）是 TRP 超家族的成员，广泛分布于中枢神经系统（CNS），在疼痛和炎症中发挥重要作用。然而，目前尚无关于 TRPA1 对癫痫发作影响的研究数据。因此，本研究旨在通过皮层脑电图（ECoG）研究 TRPA1 激动剂肉桂醛（TCA）对戊四氮（PTZ）诱导的点燃模型的亚慢性作用。此外，还通过 Western blot 法测定 cAMP 反应元件结合蛋白（CREB）、脑源性神经营养因子（BDNF）和 NMDA 受体亚单位 NR2B 的表达。通过腹腔内（i.p.）PTZ（35mg/kg）注射使大鼠产生癫痫样发作。在电极植入和愈合期后，连续 14 天 i.p.给予 10 和 30mg/kg 的 TCA。在注射 PTZ（35mg/kg，i.p.）的次日，进行 ECoG 记录，24 小时后，大鼠断头进行分子分析。30mg/kg 的 TCA 可降低首次肌阵挛发作潜伏期，并增加发作持续时间和总尖波活动。此外，两种剂量的 TCA 均可增强 CREB、BDNF 和 NR2B 的表达，而这些表达是由点燃引起的。本研究表明，TRPA1 通道的长期激活可导致癫痫发作活动加剧。此外，反复给予 TCA 可增强 PTZ 诱导的 CREB、BDNF 和 NR2B 水平升高。
