Kumar Puneet, Kumar Anil
Pharmacology Division, University Institute of Pharmaceutical Sciences, Panjab University, Chandigarh 160014, India.
Indian J Exp Biol. 2009 Sep;47(9):715-22.
Huntington's disease (HD) is an inherited progressive neurodegenerative disorder in human characterized by progressive loss of movement and cognitive disturbances. 3-nitropropionic acid (3-NP; a mitochondrial toxin) produces age-dependent oxidative linked striatal damage, responsible for HD like symptoms. In the present study protective effect of sertraline in 3-NP induced HD like symptoms was evaluated in rats. Systemic administration of 3-NP (10 mg/kg for 14 days) resulted in impairment of memory as assessed in Morris water maze and elevated plus paradigm tasks. Biochemical analysis revealed that systemic 3-NP administration significantly impaired reduced glutathione, total glutathione, oxidized glutathione and glutathione-S-transferase levels, whereas the level of acetylcholinesterase enzyme increased in striatum, cortex and hippocampus regions of rat brain. Sertraline (5 and 10 mg/kg po) treatment once daily for 14 days significantly improved cognitive performance tasks and glutathione levels in 3-NP treated group. However, combination of yohimbine (2 mg/kg) (non selective serotonin receptors antagonist) with the higher dose of sertraline (10 mg/kg) did not influence the protective action of sertraline. Result shows that neuroprotective and antioxidant like effect of sertraline is independent of its conventional action on 5-HT receptor.
亨廷顿舞蹈症（HD）是一种人类遗传性进行性神经退行性疾病，其特征为运动能力逐渐丧失和认知障碍。3-硝基丙酸（3-NP；一种线粒体毒素）会产生与年龄相关的氧化相关纹状体损伤，导致类似HD的症状。在本研究中，评估了舍曲林对3-NP诱导的大鼠类似HD症状的保护作用。全身性给予3-NP（10 mg/kg，持续14天）导致在莫里斯水迷宫和高架十字迷宫任务中评估的记忆受损。生化分析显示，全身性给予3-NP显著损害了还原型谷胱甘肽、总谷胱甘肽、氧化型谷胱甘肽和谷胱甘肽-S-转移酶水平，而大鼠脑纹状体、皮质和海马区的乙酰胆碱酯酶水平升高。舍曲林（5和10 mg/kg，口服）每天一次，持续14天，显著改善了3-NP治疗组的认知表现任务和谷胱甘肽水平。然而，育亨宾（2 mg/kg）（非选择性5-羟色胺受体拮抗剂）与较高剂量的舍曲林（10 mg/kg）联合使用并不影响舍曲林的保护作用。结果表明，舍曲林的神经保护和抗氧化样作用与其对5-羟色胺受体的传统作用无关。
