Gupta Surbhi, Sharma Bhupesh
Neuropharmacology Lab., Department of Pharmacology, School of Pharmacy, Bharat Institute of Technology, Partapur Bypass, Meerut, Uttar Pradesh, India.
Department of Pharmacology, School of Pharmacy, Bharat Institute of Technology, Partapur Bypass, Meerut, Uttar Pradesh, India; CNS Pharmacology, Conscience Research, Pocket F-233, B, Dilshad Garden, Delhi 110095, India.
Brain Res Bull. 2014 Mar;102:57-68. doi: 10.1016/j.brainresbull.2014.02.007. Epub 2014 Feb 28.
Huntington's disease (HD), a neurodegenerative disorder, is characterized by progressive motor dysfunction, emotional disturbances, dementia, weight loss and anxiety. The tremendous amount of research work is required to identify new pharmacological agents of therapeutic utility to combat this condition. This study investigates the effect of selective modulator of I1-imidazoline receptor (moxonidine) as well as nuclear factor kappa-B (NF-κB) (natrium diethyl dithio carbamate trihydrate-NDDCT) on 3-nitropropionic acid (3-NPA) induced experimental HD condition. 3-NPA was used to induce mitochondrial damage and associated HD symptoms in rats. Anxiety was assessed using Elevated plus maze-EPM and learning-memory was assessed using EPM and Morris water maze-MWM. Different biochemical estimations were used to assess brain striatum oxidative stress (lipid peroxide, superoxide dismutase and catalase), nitric oxide levels (nitrite/nitrate), cholinergic activity (brain striatum acetyl cholinesterase activity), and mitochondrial enzyme complex (I, II and IV) activities. 3-NPA has induced anxiety, impaired learning-memory with a reduction in body weight, locomotor activity, grip strength. It has increased brain striatum acetylcholinesterase-AChE activity, oxidative stress (lipid peroxide, nitrite/nitrate, superoxide dismutase and catalase) and impaired mitochondrial complex enzyme (I, II and IV) activities. Tetrabenazine-TBZ (monoamine storage inhibitor) was used as positive control. Treatment with moxonidine, NDDCT and TBZ significantly attenuated 3-NPA induced reduction in body weight, locomotor activity, grip strength, anxiety as well as impaired learning and memory. Administration of these agents attenuated 3-NPA induced various biochemical impairments. Therefore, modulation of I1-imidazoline receptor as well as NF-κB may be considered as potential pharmacological agents for the management of 3-NPA induced HD.
亨廷顿舞蹈症（HD）是一种神经退行性疾病，其特征为进行性运动功能障碍、情绪紊乱、痴呆、体重减轻和焦虑。需要开展大量研究工作来确定对抗这种疾病的具有治疗效用的新药理剂。本研究调查了1-咪唑啉受体选择性调节剂（莫索尼定）以及核因子κB（NF-κB）（三水合二乙基二硫代氨基甲酸钠-NDDCT）对3-硝基丙酸（3-NPA）诱导的实验性HD病症的影响。3-NPA用于诱导大鼠的线粒体损伤及相关HD症状。使用高架十字迷宫（EPM）评估焦虑，使用EPM和莫里斯水迷宫（MWM）评估学习记忆。采用不同的生化检测方法评估脑纹状体氧化应激（脂质过氧化物、超氧化物歧化酶和过氧化氢酶）、一氧化氮水平（亚硝酸盐/硝酸盐）、胆碱能活性（脑纹状体乙酰胆碱酯酶活性）以及线粒体酶复合体（I、II和IV）活性。3-NPA诱发了焦虑、损害了学习记忆，同时伴有体重、运动活性、握力下降。它还增加了脑纹状体乙酰胆碱酯酶（AChE）活性、氧化应激（脂质过氧化物、亚硝酸盐/硝酸盐、超氧化物歧化酶和过氧化氢酶），并损害了线粒体复合体酶（I、II和IV）活性。丁苯那嗪（TBZ）（单胺储存抑制剂）用作阳性对照。用莫索尼定、NDDCT和TBZ治疗可显著减轻3-NPA诱导的体重、运动活性、握力下降、焦虑以及学习和记忆损害。给予这些药剂可减轻3-NPA诱导的各种生化损伤。因此，调节1-咪唑啉受体以及NF-κB可被视为治疗3-NPA诱导的HD的潜在药理剂。
