Department of Neurology, Fujian Medical University Union Hospital, Xinquan Road 29#, Fuzhou, 350001, China.
Department of Neurosurgery, Fujian Provincial Hospital, Fuzhou, China.
J Mol Neurosci. 2019 Mar;67(3):388-399. doi: 10.1007/s12031-018-1238-4. Epub 2019 Jan 29.
Cognitive impairment is a common comorbidity in patients with temporal lobe epilepsy (TLE) that severely affects patients' quality of life. Also, serotonin 5-hydroxytryptamine 6 (5-HT6) receptor plays an important role in cognition. This study aimed to investigate effects of 5-HT6 receptor on learning-memory capacities in epileptic rats. Total of 36 adult Sprague-Dawley (SD) rats were divided into vehicle (n = 6) and epileptic group (n = 30). Status epilepticus (SE) was induced via systemic injection of pilocarpine. Epileptic group was sub-divided into vehicle, 10, 20, and 30 μg SB-271046 groups, six mice per group. Learning-memory performance of rats was evaluated by using Y maze and Morris water maze test. 5-HT6 receptor expression was examined using immunostaining and Western blot. The other six rats were used to make epileptic model and Jab-1/p-c-Jun were detected. Results showed that frequency of spontaneous recurrent seizures (SRSs) was significantly decreased in pilocarpine-induced epileptic rats that treated with SB-271046. Alternation rate and new arm percentage were decreased in epileptic rats compared to control. The 5-day mean latency was prolonged in epileptic rats compared to control rats. During retention stage, mean latency, number of target crossings, and percentage of time spent in target zone were decreased in epileptic rats, but not in those treated with SB-271046. The number of apoptotic neurons was significantly increased in epileptic rats, which was decreased by SB-271046. 5-HT6 expression was significantly increased in hippocampus and cortex following recurrent seizures. Jab-1 level was decreased after SB-271046 administration. p-c-Jun level was elevated in epileptic rats and decreased in a dose-dependent manner after the SB-271046 administration. In conclusion, the over-expression of 5-HT6 receptor and activated Jab-1/p-c-Jun plays an important role in pilocarpine-induced seizures and learning-memory impairment.
认知障碍是颞叶癫痫（TLE）患者常见的合并症，严重影响患者的生活质量。此外，血清素 5-羟色胺 6（5-HT6）受体在认知中起重要作用。本研究旨在探讨 5-HT6 受体对癫痫大鼠学习记忆能力的影响。将 36 只成年 Sprague-Dawley（SD）大鼠分为对照组（n=6）和癫痫组（n=30）。通过腹腔注射匹罗卡品诱导癫痫持续状态（SE）。癫痫组进一步分为对照组、10、20 和 30μg SB-271046 组，每组 6 只。使用 Y 迷宫和 Morris 水迷宫测试评估大鼠的学习记忆能力。免疫染色和 Western blot 检测 5-HT6 受体的表达。另外 6 只大鼠用于制作癫痫模型，并检测 Jab-1/p-c-Jun。结果显示，匹罗卡品诱导的癫痫大鼠中，SB-271046 治疗后自发性复发发作（SRSs）的频率显著降低。与对照组相比，癫痫大鼠的交替率和新臂百分比降低。与对照组大鼠相比，癫痫大鼠的 5 天平均潜伏期延长。在保留阶段，与对照组相比，癫痫大鼠的平均潜伏期、目标穿越次数和目标区域时间百分比减少，但 SB-271046 治疗组大鼠无变化。癫痫大鼠的神经元凋亡数量显著增加，SB-271046 治疗后减少。海马和皮质中 5-HT6 表达在反复发作后显著增加。SB-271046 给药后 Jab-1 水平降低。p-c-Jun 水平在癫痫大鼠中升高，并呈剂量依赖性降低。综上所述，5-HT6 受体的过度表达和激活的 Jab-1/p-c-Jun 在匹罗卡品诱导的癫痫发作和学习记忆障碍中起重要作用。
