Hasbani Daphne M, Perez Francisco A, Palmiter Richard D, O'Malley Karen L
Department of Anatomy and Neurobiology, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
J Neurosci. 2005 Oct 12;25(41):9428-33. doi: 10.1523/JNEUROSCI.0130-05.2005.
Dopamine (DA) has been postulated to play a role in the loss of dopaminergic substantia nigra (SN) neurons in Parkinson's disease because of its propensity to oxidize and form quinones and other reactive oxygen species that can alter cellular function. Moreover, DA depletion can attenuate dopaminergic cell loss in vitro. To test the contribution of DA to SN impairment in vivo, we used DA-deficient mice, which lack the enzyme tyrosine hydroxylase in dopaminergic cells, and mice pharmacologically depleted of DA by alpha-methyl-p-tyrosine pretreatment. Mice were treated with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), a toxin that produces parkinsonian pathology in humans, nonhuman primates, and rodents. In contrast to in vitro results, genetic or pharmacologic DA depletion did not attenuate loss of dopaminergic neurons in the SN or dopaminergic neuron terminals in the striatum. These results suggest that DA does not contribute to acute MPTP toxicity in vivo.
多巴胺（DA）被推测在帕金森病中黑质多巴胺能神经元的丢失中起作用，因为它易于氧化并形成醌类和其他活性氧物质，这些物质可改变细胞功能。此外，多巴胺耗竭可在体外减轻多巴胺能细胞的损失。为了测试多巴胺对体内黑质损伤的作用，我们使用了多巴胺能细胞中缺乏酪氨酸羟化酶的多巴胺缺乏小鼠，以及通过α-甲基对酪氨酸预处理在药理学上耗尽多巴胺的小鼠。用1-甲基-4-苯基-1,2,3,6-四氢吡啶（MPTP）处理小鼠，MPTP是一种在人类、非人灵长类动物和啮齿动物中产生帕金森病病理的毒素。与体外结果相反，基因或药理学上的多巴胺耗竭并没有减轻黑质中多巴胺能神经元或纹状体中多巴胺能神经元终末的损失。这些结果表明，多巴胺对体内急性MPTP毒性没有作用。
