Wang Bo, Jin Xin, Kuang Xin, Tian Shaowen
Department of Anesthesiology, First Affiliated Hospital, University of South China, Hengyang, Hunan, 421001, People's Republic of China.
Department of Anesthesiology, Nanhua Affiliated Hospital, University of South China, Hengyang, Hunan, 421001, People's Republic of China.
BMC Anesthesiol. 2017 Nov 13;17(1):152. doi: 10.1186/s12871-017-0443-y.
Previous studies have shown that cyclooxygenase-2, a key enzyme that converts arachidonic acid to prostaglandins, is involved in anxiety and cognitive processes, but few studies have investigated the effects of chronic administration of cyclooxygenase-2 inhibitors on anxiety, learning and memory under normal physiological conditions. The aim of the study was to investigate the effects of chronic administration of parecoxib, a cyclooxygenase-2 inhibitor, on anxiety behavior and memory performance under normal physiological conditions and to explore the possible neural mechanism underlying parecoxib-mediated effects.
Adult male ICR mice were randomly divided into four groups: the control group and three parecoxib groups. Mice received normal saline or parecoxib (2.5, 5.0 or 10 mg/kg) intraperitoneal injection once a day for 21 days, respectively. Elevated plus-maze, novel object recognition and Y maze tests were conducted on day 23, 24 and 26, respectively. Four additional groups that received same drug treatment were used to measure synaptophysin protein levels by western blot and prostaglandin E2 (PGE2) levels by ELISA in the amygdala and hippocampus on day 26.
Chronic parecoxib exerted an anxiolytic-like effect in the plus-maze test test, and enhanced memory performance in the novel object recognition and Y maze tests. Western blot analysis showed that chronic parecoxib down-regulated synaptophysin levels in the amygdala and up-regulated synaptophysin levels in the hippocampus. ELISA assay showed that chronic parecoxib inhibited PGE2 in the hippocampus but not amygdala.
Chronic parecoxib exerts anxiolytic-like and memory enhancing effects, which might be mediated through differential modulation of synaptophysin and PGE2 in the amygdala and hippocampus.
先前的研究表明，环氧化酶-2作为一种将花生四烯酸转化为前列腺素的关键酶，参与焦虑和认知过程，但很少有研究在正常生理条件下调查长期给予环氧化酶-2抑制剂对焦虑、学习和记忆的影响。本研究的目的是调查环氧化酶-2抑制剂帕瑞昔布长期给药在正常生理条件下对焦虑行为和记忆表现的影响，并探索帕瑞昔布介导作用的潜在神经机制。
成年雄性ICR小鼠随机分为四组：对照组和三个帕瑞昔布组。小鼠分别每天腹腔注射生理盐水或帕瑞昔布（2.5、5.0或10mg/kg），持续21天。分别在第23、24和26天进行高架十字迷宫、新物体识别和Y迷宫测试。另外四个接受相同药物治疗的组在第26天通过蛋白质免疫印迹法测量杏仁核和海马体中突触素蛋白水平，并通过酶联免疫吸附测定法测量前列腺素E2（PGE2）水平。
长期给予帕瑞昔布在高架十字迷宫测试中产生抗焦虑样作用，并在新物体识别和Y迷宫测试中增强记忆表现。蛋白质免疫印迹分析表明，长期给予帕瑞昔布可下调杏仁核中突触素水平，并上调海马体中突触素水平。酶联免疫吸附测定显示，长期给予帕瑞昔布可抑制海马体而非杏仁核中的PGE2。
长期给予帕瑞昔布具有抗焦虑样和增强记忆的作用，这可能是通过对杏仁核和海马体中突触素和PGE2的差异调节介导的。
