Kalonia Harikesh, Kumar Puneet, Nehru Bimla, Kumar Anil
Pharmacology Division, University Institute of Pharmaceutical Sciences, UGC Centre for Advanced Studies, Panjab University, Chandigarh 160 014, India.
Indian J Exp Biol. 2009 Nov;47(11):880-92.
Huntington's Disease (HD) is a common neurodegenerative disorder characterized by motor disturbances, subcortical dementia and psychiatric disturbances. Pathogenesis of HD revolves so far around excitatory amino acids as the primary cause of neuronal loss. However, number of recent reports suggests the involvement of excitotoxicity and oxidative damage. In the present study, first the dose of quinolinic acid that mimics the symptoms of HD was standardized and then the neuroprotective effect of MK-801 (noncompetitive NMDAr antagonist) was evaluated against intrastriatal quinolinic acid induced behavioral, oxidative stress and cellular alterations in rats. A single unilateral (ipsilateral striatum) injections of quinolinic acid (100, 200 and 300 nM) were made in to striatum. Animals were tested for motor functions using actophotometer and rotarod apparatus. Quinolinic acid (300 nM) significantly reduced the body weight and caused motor in-coordination and produced oxidative damage in the cortex and striatum as indicated by raised lipid peroxidation, nitrite concentration, depletion of superoxide dismutase, catalase and different glutathione levels. Beside, quinolinic acid (300 nM) significantly altered the mitochondrial enzymes complex levels and caused histopathological alterations in the striatum. MK-801(0.02, 0.04, 0.08 mg/kg, ip) treatment significantly improved body weight, behavioral alterations (locomotor activity and rotarod performance) and attenuated oxidative damage and mitochondrial enzymes complex dysfunction. Besides, MK-801 treatment significantly reversed histopathological alterations in striatum. The results suggest antioxidant and neuroprotective action of MK-801 against the quinolinic acid induced Huntington's like behavioral, oxidative stress and cellular alterations in rats.
亨廷顿舞蹈症（HD）是一种常见的神经退行性疾病，其特征为运动障碍、皮质下痴呆和精神障碍。迄今为止，HD的发病机制主要围绕兴奋性氨基酸作为神经元丧失的主要原因。然而，最近的一些报道表明兴奋毒性和氧化损伤也与之有关。在本研究中，首先对模拟HD症状的喹啉酸剂量进行了标准化，然后评估了MK-801（非竞争性NMDAr拮抗剂）对纹状体内注射喹啉酸诱导的大鼠行为、氧化应激和细胞改变的神经保护作用。向纹状体进行单次单侧（同侧纹状体）注射喹啉酸（100、200和300 nM）。使用光电计和转棒仪对动物的运动功能进行测试。喹啉酸（300 nM）显著降低体重，导致运动不协调，并在皮质和纹状体中产生氧化损伤，表现为脂质过氧化增加、亚硝酸盐浓度升高、超氧化物歧化酶、过氧化氢酶和不同谷胱甘肽水平的消耗。此外，喹啉酸（300 nM）显著改变线粒体酶复合物水平，并导致纹状体的组织病理学改变。MK-801（0.02、0.04、0.08 mg/kg，腹腔注射）治疗显著改善体重、行为改变（运动活动和转棒性能），并减轻氧化损伤和线粒体酶复合物功能障碍。此外，MK-801治疗显著逆转了纹状体的组织病理学改变。结果表明，MK-801对喹啉酸诱导的大鼠类似亨廷顿舞蹈症的行为、氧化应激和细胞改变具有抗氧化和神经保护作用。
