Huang Qing-Yuan, Yu Liqun, Ferrante Robert J, Chen Jiang-Fan
Department of Neurology, Boston University School of Medicine, 715 Albany Street, E301 Boston, MA, USA.
Neurosci Lett. 2007 May 17;418(2):175-80. doi: 10.1016/j.neulet.2007.03.038. Epub 2007 Mar 21.
3-Nitropropionic acid (3-NP), an irreversible inhibitor of succinate dehydrogenase, produces selective lesions in striatal neurons that resemble those observed in Huntington's disease neuropathology. In this study, we evaluated the role of peripheral bone marrow-derived cells (BMDCs) in the 3-NP-induced striatal damage by transplanting bone marrow cells with human SOD1 G93A mutation (mSOD1(G93A)) which induces amyotrophic lateral sclerosis through an unknown gain of toxicity and mitochondrial dysfunction. We assessed striatal damage after 3-NP treatment in the recipient C57BL/6 wild-type (WT) mice that received bone marrow cells from WT or mSOD1(G93A) transgenic donor mice (WT-->WT or mSOD(G93A)-->WT). After intraperitoneal injection of 3-NP, six of the eight mSOD1(G93A)-->WT mice had bilateral striatal lesions while only one out of eight WT-->WT mice had a striatal lesion. The lesion volume was significantly higher in the mSOD1(G93A)-->WT mice than in the WT-->WT mice. However, following an intrastriatal injection of 3-NP, there was no significant difference in the lesion volumes between the WT-->WT mice and mSOD1(G93A)-->WT mice. Thus, the exacerbation of 3-NP-induced striatal damage in mSOD(G93A)-->WT mice was only seen after systemic administration of 3-NP, but not after intrastriatal injection. These results demonstrate that altered SOD1 activity (mSOD(G93A)) in BMDCs affects striatal damage probably through a mechanism involving a systemic factor.
3-硝基丙酸（3-NP）是琥珀酸脱氢酶的不可逆抑制剂，可在纹状体神经元中产生选择性损伤，类似于在亨廷顿病神经病理学中观察到的损伤。在本研究中，我们通过移植携带人类SOD1 G93A突变（mSOD1(G93A)）的骨髓细胞来评估外周骨髓来源细胞（BMDCs）在3-NP诱导的纹状体损伤中的作用，该突变通过未知的毒性增加和线粒体功能障碍诱导肌萎缩侧索硬化症。我们评估了接受来自野生型（WT）或mSOD1(G93A)转基因供体小鼠（WT-->WT或mSOD(G93A)-->WT）骨髓细胞的受体C57BL/6野生型（WT）小鼠在3-NP处理后的纹状体损伤情况。腹腔注射3-NP后，八只mSOD1(G93A)-->WT小鼠中有六只出现双侧纹状体损伤，而八只WT-->WT小鼠中只有一只出现纹状体损伤。mSOD1(G93A)-->WT小鼠的损伤体积显著高于WT-->WT小鼠。然而，纹状体内注射3-NP后，WT-->WT小鼠和mSOD1(G93A)-->WT小鼠的损伤体积没有显著差异。因此，mSOD(G93A)-->WT小鼠中3-NP诱导的纹状体损伤加重仅在全身给予3-NP后出现，而在纹状体内注射后未出现。这些结果表明，BMDCs中SOD1活性改变（mSOD(G93A)）可能通过涉及全身因素的机制影响纹状体损伤。
