Brouillet Emmanuel
Neurodegenerative Diseases Laboratory, URA2210, CEA, and CNRS, Molecular Imaging Research Center (MIRCen), I2BM, Life Science Division, Fontenay-aux-Roses, France.
Curr Protoc Neurosci. 2014 Apr 10;67:9.48.1-9.48.14. doi: 10.1002/0471142301.ns0948s67.
The mitochondrial toxin 3-nitropropionic acid (3-NP) is an irreversible inhibitor of respiratory chain complex II. Chronic systemic administration of 3-NP to mice, rats, and non-human primates leads to preferential degeneration of the striatum, and produces motor and cognitive symptoms that are highly reminiscent of Huntington's disease (HD). HD is caused by a dominant inherited expansion of CAG repeats in the Huntington gene. Thus, many aspects of HD cannot be mimicked by 3-NP. However, recent research shows that mitochondrial defects and oxidative stress may play a key role in HD pathogenesis, further supporting the potential utility of the 3-NP model of striatal degeneration. First, a basic protocol to produce acute striatal lesions in rats using repeated intraperitoneal injection of 3-NP is described. Second, a more complex protocol that takes advantage of the use of osmotic minipumps to steadily release 3-NP leading to consistent lesions and motor symptoms in Lewis rats is presented.
线粒体毒素3-硝基丙酸（3-NP）是呼吸链复合物II的不可逆抑制剂。对小鼠、大鼠和非人类灵长类动物长期进行全身性给予3-NP会导致纹状体优先退化，并产生与亨廷顿舞蹈病（HD）极为相似的运动和认知症状。HD是由亨廷顿基因中CAG重复序列的显性遗传扩增引起的。因此，HD的许多方面无法被3-NP模拟。然而，最近的研究表明，线粒体缺陷和氧化应激可能在HD发病机制中起关键作用，这进一步支持了3-NP诱导纹状体退化模型的潜在效用。首先，描述了一种通过反复腹腔注射3-NP在大鼠中产生急性纹状体损伤的基本方案。其次，提出了一种更复杂的方案，该方案利用渗透微型泵持续释放3-NP，从而在Lewis大鼠中导致一致的损伤和运动症状。
