中国神经再生研究(英文版) ›› 2017, Vol. 12 ›› Issue (2): 290-300.doi: 10.4103/1673-5374.200812

• 原著:退行性病与再生 • 上一篇    下一篇

腺苷酸环化酶激活对亨廷顿病样退变神经元的保护

  

  • 收稿日期:2017-01-16 出版日期:2017-02-15 发布日期:2017-02-15

Adenyl cyclase activator forskolin protects against Huntington’s disease-like neurodegenerative disorders

Sidharth Mehan, Shaba Parveen, Sanjeev Kalra   

  1. Department of Pharamcology, Rajendra Institute of Technology & Sciences, Sirsa, Haryana, India
  • Received:2017-01-16 Online:2017-02-15 Published:2017-02-15
  • Contact: Sidharth Mehan, Ph.D.,sidh.mehan@gmail.com.

摘要:

 

选择性抑制剂3-硝基丙酸对线粒体功能标志物琥珀酸脱氢酶的长程抑制已成为制备亨廷顿病啮齿类动物模型的常用方法,在该模型中线粒体功能障碍和氧化损伤是神经元损伤的主要病理标志。为验证腺苷酸环化酶激活剂毛喉素可减轻神经元兴奋性毒性损伤。实验以10 mg/kg剂量给予大鼠腹腔注射3-硝基丙酸连续15d,发现大鼠体质量、运动功能、学习和记忆功能明显下降;纹状体、大脑皮质和海马乙酰胆碱酯酶、乳酸脱氢酶、亚硝酸盐、丙二醛水平明显上升,而琥珀酸脱氢酶、三磷酸腺苷、超氧化物歧化酶、过氧化氢酶和谷胱甘肽水平明显下降,病理学改变明显。10, 20和30 mg/kg毛喉素灌胃干预剂量依赖性地逆转上述变化,从而表明毛喉素对3-硝基丙酸诱导的亨廷顿病样神经退行性变有神经保护作用。


ORCID:0000-0003-0034-835X(Sidharth Mehan)

关键词: 神经再生, 亨廷顿病, 线粒体, 腺苷酸环化酶, 毛喉素, 氧化应激, 神经退行性变

Abstract:

Long term suppression of succinate dehydrogenase by selective inhibitor 3-nitropropionic acid has been used in rodents to model Huntington’s disease where mitochondrial dysfunction and oxidative damages are primary pathological hallmarks for neuronal damage. Improvements in learning and memory abilities, recovery of energy levels, and reduction of excitotoxicity damage can be achieved through activation of Adenyl cyclase enzyme by a specific phytochemical forskolin. In this study, intraperitoneal administration of 10 mg/kg 3-nitropropionic acid for 15 days in rats notably reduced body weight, worsened motor cocordination (grip strength, beam crossing task, locomotor activity), resulted in learning and memory deficits, greatly increased acetylcholinesterase, lactate dehydrogenase, nitrite, and malondialdehyde levels, obviously decreased adenosine triphosphate, succinate dehydrogenase, superoxide dismutase, catalase, and reduced glutathione levels in the striatum, cortex and hippocampus. Intragastric administration of forskolin at 10, 20, 30 mg/kg dose-dependently reversed these behavioral, biochemical and pathological changes caused by 3-nitropropionic acid. These results suggest that forskolin exhibits neuroprotective effects on 3-nitropropionic acid-induced Huntington’s disease-like neurodegeneration.

Key words: nerve regeneration, Huntington’s disease, mitochondria, adenyl cyclase, forskolin, oxidative stress, basal ganglia, neural regeneration