Over-expression of 5-HT6 Receptor and Activated Jab-1/p-c-Jun Play Important Roles in Pilocarpine-Induced Seizures and Learning-Memory Impairment
Over-expression of 5-HT6 Receptor and Activated Jab-1/p-c-Jun Play Important Roles in Pilocarpine-Induced Seizures and Learning-Memory Impairment
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5-HT6 受体的过度表达和激活的 Jab-1/p-c-Jun 在毛果芸香碱诱发的癫痫发作和学习记忆障碍中发挥重要作用
DOI：
10.1007/s12031-018-1238-4
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发表时间：
2019-03-01
影响因子：
3.1
通讯作者：
Ma, Ying
中科院分区：
文献类型：
--
作者：
Liu, Changyun;Wen, Yuxing;Ma, Ying
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，5-羟色胺6（5-HT 6）受体在认知中起重要作用。本研究旨在探讨5-HT 6受体对癫痫大鼠学习记忆能力的影响。成年SD大鼠36只，随机分为对照组（n=6）和癫痫组（n=30）。通过全身注射匹罗卡品诱导癫痫持续状态（SE）。癫痫组再分为溶媒、10、20和30 g SB-271046组，每组6只小鼠。采用Y迷宫和Morris水迷宫实验评价大鼠学习记忆能力。免疫组化和Western blot检测5-HT 6受体表达。另6只大鼠制作癫痫模型，检测Jab-1/p-c-Jun。结果显示，SB-271046处理的匹罗卡品诱导的癫痫大鼠的自发性复发性癫痫发作（SRS）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。在保持阶段，癫痫大鼠的平均潜伏期、目标交叉次数和在目标区花费的时间百分比降低，但SB-271046处理组未降低。癫痫大鼠凋亡神经元数量显著增加，SB-271046可减少凋亡神经元数量。反复发作后海马和皮层5-HT 6表达显著增加。SB-271046给药后Jab-1水平降低。癫痫大鼠中p-c-Jun水平升高，SB-271046给药后以剂量依赖性方式降低。结论：5-HT 6受体的过度表达和Jab-1/p-c-Jun的激活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。
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 30g 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.