Uncoupling protein-2 promotes nigrostriatal dopamine neuronal function
Uncoupling protein-2 promotes nigrostriatal dopamine neuronal function
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DOI：
10.1111/j.1460-9568.2006.04906.x
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发表时间：
2006-07-01
影响因子：
3.4
通讯作者：
Horvath, Tamas L.
中科院分区：
文献类型：
--
作者：
Andrews, Zane B.;Rivera, Alicia;Horvath, Tamas L.
已知解偶联蛋白2（UCP 2）在包括帕金森病在内的许多形式的神经病理学中促进神经保护。在这里，我们研究了UCP 2也介导正常黑质纹状体多巴胺（DA）功能的假设。缺乏UCP 2的小鼠表现出纹状体中的多巴胺周转减少，如通过3，4-二羟基苯乙酸/多巴胺（DOPAC/DA）比率测量的，黑质腹侧部（SNc）和网状部、纹状体和背侧核中的酪氨酸羟化酶免疫反应性（TH IR）减少。UCP 2敲除（KO）小鼠的SNc中多巴胺转运蛋白免疫反应性（DAT IR）也降低，但未检测到其他脑区。为了确定这些生化缺陷是否转录为行为缺陷，我们检查了UCP 2-KO小鼠与野生型（WT）对照相比的运动功能。与野生型对照相比，UCP 2-KO小鼠表现出显著减少的总运动距离、运动速度和增加的休息时间。这些结果表明，UCP 2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，UCP 2水平的降低可能使个体易患帕金森病的环境原因。
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.