Ranju Vijayan, Sathiya Sekar, Kalaivani Periyathambi, Priya Raju Jyothi, Saravana Babu Chidambaram
Centre for Toxicology and Developmental Research, Sri Ramachandra University, Chennai 600116, India; Department of Biotechnology, Dr. M.G.R. Educational and Research Institute, Maduravoyal, Chennai 600095, India.
Centre for Toxicology and Developmental Research, Sri Ramachandra University, Chennai 600116, India.
Neurosci Lett. 2015 Jan 23;586:1-7. doi: 10.1016/j.neulet.2014.11.036. Epub 2014 Dec 2.
Memantine (MN), a NMDA blocker is well known for its protective effect against various neurodegenerative diseases. However, its role in improving motor function and regulation of neurotrophic factors in Huntington's disease (HD) has not been studied yet. In the present study, we have investigated the effect of MN against 3-nitropropionic acid (3NP), induced motor impairment, and alterations in the expression of brain-derived neurotrophic factor (BDNF) and glial cell-derived neurotrophic factor (GDNF) in mice brain. Further, its role in mitochondrial function was assessed by measuring succinate dehydrogenase (SDH) activity. Glial fibrillary acidic protein (GFAP) and neuronal nuclei (NeuN) immunoreactivity were studied to evaluate the role of MN on glial and neuronal function. Its effect on apoptosis was adjudged by studying the expression of apoptotic markers. MN restored motor functions with an associated up-regulation in neurotrophin expression. MN also enhanced brain SDH activity and decreased glutamate content. MN ameliorated striatal neuronal loss, reduced GFAP immunoreactivity, and exhibited protective effect against neuronal apoptosis. Data from the current study demonstrated that MN exerted neuroprotective effect against 3NP induced neuropathology. Restoration of motor function by MN might be through regulation of neurotrophin expression. MN can therefore be a useful therapeutic choice in the symptomatic management of HD.
美金刚（MN）是一种N-甲基-D-天冬氨酸（NMDA）受体拮抗剂，因其对各种神经退行性疾病的保护作用而闻名。然而，其在改善亨廷顿舞蹈病（HD）运动功能及调节神经营养因子方面的作用尚未得到研究。在本研究中，我们研究了美金刚对3-硝基丙酸（3NP）诱导的小鼠运动障碍以及脑源性神经营养因子（BDNF）和胶质细胞源性神经营养因子（GDNF）在小鼠脑内表达变化的影响。此外，通过测量琥珀酸脱氢酶（SDH）活性评估了其在线粒体功能中的作用。研究了胶质纤维酸性蛋白（GFAP）和神经元核抗原（NeuN）的免疫反应性，以评估美金刚对神经胶质和神经元功能的作用。通过研究凋亡标志物的表达来判断其对细胞凋亡的影响。美金刚恢复了运动功能，同时神经营养因子表达上调。美金刚还增强了脑内SDH活性并降低了谷氨酸含量。美金刚改善了纹状体神经元损失，降低了GFAP免疫反应性，并对神经元凋亡表现出保护作用。本研究数据表明，美金刚对3NP诱导的神经病理学具有神经保护作用。美金刚恢复运动功能可能是通过调节神经营养因子的表达实现的。因此，美金刚可能是HD症状管理中一种有用的治疗选择。
