氟吡汀抗3-NPA诱导的亨廷顿病实验模型记忆障碍和运动不协调的新神经保护机制

YMER Digital Pub Date : 2022-08-17 DOI:10.37896/ymer21.08/53
Rubi Rani, Mansi Aggarwal, Aakash Jaiswal
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摘要

亨廷顿氏病(HD)是一种进行性神经退行性疾病,患者的认知能力逐渐下降,记忆力和正常运动能力受损。亨廷顿病(HD)是由亨廷顿蛋白基因(Htt) 4p16.3染色体短臂上CAG重复序列重复引起的常染色体显性遗传性疾病。在Morris水迷宫测试中,3-NPA处理组大鼠比对照组和氟吡汀组更快地找到平台,即空间记忆和学习记忆都比对照组大鼠多。3-NPA组与氟吡汀组在Probe试验当天的差异有统计学意义。氟吡汀高剂量组大鼠在开放臂的时间比3-NPA处理大鼠长,在暗臂的时间比3-NPA处理大鼠短。与对照组相比,3-NPA在旋转棒上的滞留时间减少,氟吡汀高剂量处理大鼠在旋转棒上的滞留时间增加。与对照组相比,3-NPA处理组大鼠GSH水平降低,高剂量氟吡汀使3-NPA处理组大鼠GSH水平升高。3-NPA大鼠丙二醛含量高于对照组,氟吡汀治疗组丙二醛含量较低。氟吡汀可使3- NPA处理大鼠体内SOD水平升高,而SOD水平因3- NPA毒性作用而降低。与对照组相比,3- NPA处理大鼠的CAT水平较低,氟吡汀使3- NPA处理大鼠的CAT水平升高。关键词:亨廷顿氏病,氟吡汀,Morris水迷宫试验,亨廷顿基因,3-硝基丙酸,神经退行性疾病
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Novel Neuro protective mechanism of Flupirtine against 3-NPA induced memory impairment and motor incoordination in experimental model of Huntington’s disease.
Huntington’s Disease (HD) is a progressive neurodegenerative disorder that gradually declines cognitive skills, impair memory and normal movements of affected individuals. Huntington’s Disease (HD) is an autosomal dominant inherited disease caused by the repetition of CAG repeats on the short arm of chromosome 4p16.3 in huntingtin gene (Htt). On the Morris Water Maze test, 3-NPA treated group rats finds the platform in less time than control & Flupirtine group i.e. their spatial & learning memory was more than control group rats. The significant difference was found at Probe trial day between 3-NPA and Flupirtine group. Flupirtine treated rats at high dose spent more time in open arm than 3-NPA treated rats and less time in dark arm then 3-NPA treated rats. 3-NPA showed decreased retention time on the rotating rod than the control group & Flupirtine at high dose treated rats showed increased retention time on the rotating rod. Decreased GSH levels were observed in 3-NPA treated group than control group rats and Flupirtine at high dose increased the level of GSH in 3- NPA treated rats. High level of MDA was found in 3-NPA rats than control group rats and found to be low in the Flupirtine treated group. Flupirtine increase the level of SOD in 3- NPA treated rats as it was reduced due to the toxicity of 3- NPA. Low levels of CAT were also observed in 3- NPA treated rats compared to control group and Flupirtine increases the level of CAT in 3- NPA treated rats. Keywords: Huntington’s Disease, Flupirtine, Morris Water Maze test, huntingtin gene, 3- Nitropropanoic acid (3-NPA), neurodegenerative disorder.
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