Fillebeen C, Mitchell V, Dexter D, Benaissa M, Beauvillain J, Spik G, Pierce A
Laboratoire de Chimie Biologique, UMR CNRS 8576, Université des Sciences et Technologies de Lille, F-59655 Villeneuve d'Ascq Cedex, France.
Brain Res Mol Brain Res. 1999 Oct 1;72(2):183-94. doi: 10.1016/s0169-328x(99)00221-1.
The presence of iron in brain tissue in increased concentrations in Parkinson's disease cases, where it might be responsible for oxidative stress, and the parallel observation that the iron transporter lactoferrin (Lf) was present in increased amounts in surviving neurons, led us to study the synthesis of Lf in a mouse model of Parkinson's disease. In this context, the origin and expression of brain Lf in normal, aged and MPTP (1-methyl-4-phenyl-1, 2,3,6-tetrahydropyridine)-treated mice were investigated. Lf immunostaining was observed mainly on microvessels in the cerebral cortex of the adult mice and to a greater extent in older mice. Lf immunoreactivity was also present in the hippocampus only in the aged mouse brains, associated with structures which seemed to be pyramidal neurons and fibers. After RT-PCR (polymerase chain reaction), Lf transcripts were found in mouse brain tissue whatever the age of the animals studied but the level of their expression was very low. No up-regulation of Lf was detectable during aging. Lf distribution and expression in the MPTP-induced Parkinsonian mouse model were also investigated. A marked depletion of dopamine (DA) occurred in the high dose MPTP-treated mice. The level of Lf expression was found to be markedly increased in the same animals and this up-regulation occurred on the first day after MPTP administration. When the brain was stressed by the neurotoxin MPTP, Lf expression increased in line with antioxidant enzymes such as catalase and gamma-glutamylcysteine synthetase, which may permit the protection of brain tissue from oxidative damage induced by the drug.
在帕金森病患者的脑组织中，铁的浓度升高，铁可能是氧化应激的诱因。同时，有平行观察发现，存活神经元中铁转运蛋白乳铁蛋白（Lf）的含量也有所增加。基于此，我们在帕金森病小鼠模型中研究了Lf的合成。在此背景下，我们对正常、老龄以及经1-甲基-4-苯基-1,2,3,6-四氢吡啶（MPTP）处理的小鼠脑组织中Lf的来源及表达情况进行了研究。Lf免疫染色主要见于成年小鼠大脑皮质的微血管，在老龄小鼠中更为明显。Lf免疫反应性也仅在老龄小鼠的海马体中出现，与似乎是锥体神经元和纤维的结构相关。经逆转录聚合酶链反应（RT-PCR）检测，无论所研究动物的年龄如何，在小鼠脑组织中均发现了Lf转录本，但其表达水平非常低。在衰老过程中未检测到Lf的上调。我们还研究了Lf在MPTP诱导的帕金森病小鼠模型中的分布及表达情况。高剂量MPTP处理的小鼠出现了明显的多巴胺（DA）耗竭。在同一批动物中发现Lf表达水平显著升高，且这种上调在MPTP给药后的第一天就出现了。当大脑受到神经毒素MPTP的刺激时，Lf的表达与过氧化氢酶和γ-谷氨酰半胱氨酸合成酶等抗氧化酶一致增加，这可能有助于保护脑组织免受该药物诱导的氧化损伤。
