Andrews Zane B, Rivera Alicia, Elsworth John D, Roth Robert H, Agnati Luigi, Gago Belen, Abizaid Alfonso, Schwartz Michael, Fuxe Kjell, Horvath Tamas L
Department of Obstetrics, Gynecology & Reproductive Services, Yale University School of Medicine, New Haven, CT 06510, USA.
Eur J Neurosci. 2006 Jul;24(1):32-6. doi: 10.1111/j.1460-9568.2006.04906.x.
Uncoupling protein 2 (UCP2) is known to promote neuroprotection in many forms of neurological pathologies including Parkinson's disease. Here, we examined the hypothesis that UCP2 also mediates aspects of normal nigrostriatal dopamine (DA) function. Mice lacking UCP2 exhibited reduced dopamine turnover in the striatum as measured by the 3,4-dihydoxyphenylacetic acid/dopamine (DOPAC/DA) ratio, reduced tyrosine hydroxylase immunoreactivity (TH IR) in the substantia nigra pars compacta (SNc) and reticulata, striatum and nucleus accumbens. UCP2-knockout (KO) mice also had reduced dopamine transporter immunoreactivity (DAT IR) in the SNc but not other brain regions examined. In order to determine if these biochemical deficits are transcribed into behavioural deficits, we examined locomotor function in UCP2-KO mice compared to wild-type (WT) controls. UCP2-KO mice exhibited significantly reduced total movement distance, movement velocity and increased rest time compared to wild-type controls. These results suggest that UCP2 is an important mitochondrial protein that helps to maintain normal nigrostriatal dopamine neuronal function and a reduction in UCP2 levels may predispose individuals to environmental causes of Parkinson's disease.
已知解偶联蛋白2（UCP2）在包括帕金森病在内的多种神经病理学形式中促进神经保护作用。在此，我们检验了UCP2也介导正常黑质纹状体多巴胺（DA）功能的某些方面这一假说。通过3,4-二羟基苯乙酸/多巴胺（DOPAC/DA）比值测量，缺乏UCP2的小鼠纹状体中的多巴胺周转率降低，黑质致密部（SNc）、黑质网状部、纹状体和伏隔核中的酪氨酸羟化酶免疫反应性（TH IR）降低。UCP2基因敲除（KO）小鼠的SNc中的多巴胺转运体免疫反应性（DAT IR）也降低，但在所检查的其他脑区中未降低。为了确定这些生化缺陷是否转化为行为缺陷，我们比较了UCP2-KO小鼠与野生型（WT）对照的运动功能。与野生型对照相比，UCP2-KO小鼠的总移动距离、移动速度显著降低，休息时间增加。这些结果表明，UCP2是一种重要的线粒体蛋白，有助于维持正常的黑质纹状体多巴胺神经元功能，UCP2水平降低可能使个体易患帕金森病的环境病因。
