Connor J R, Snyder B S, Beard J L, Fine R E, Mufson E J
Department of Neuroscience and Anatomy, Pennsylvania State University College of Medicine, M.S. Hershey Medical Center, Hershey 17033.
J Neurosci Res. 1992 Feb;31(2):327-35. doi: 10.1002/jnr.490310214.
It is well established that iron, which is of considerable importance for normal neurological function, is highly regulated in all organ systems. However, until recently, iron regulation in the nervous system has received little attention. This study quantitatively compares the levels of the major iron-regulatory proteins, transferrin and ferritin, and iron itself in three cerebral cortical regions of the human brain from material collected at autopsy. Three groups were studied: 1) normal adult (under 65 yr of age), 2) aged (greater than 65), and 3) Alzheimer's disease. Normally, transferrin is more abundant in white matter than in gray matter. Ferritin is approximately 10x more abundant than transferrin throughout the brain regions examined and is evenly distributed, as is iron, in the gray and white matter. In Alzheimer's disease transferrin is consistently decreased particularly in the white matter of the various cerebral cortical regions examined whereas the iron and ferritin changes are inconsistent. The observations in this study are consistent with our general hypothesis that iron homeostasis is disrupted in the aging brain and the alterations in iron-regulatory proteins are exacerbated in Alzheimer's disease. The decrease in transferrin levels could indicate a decreased mobility and subsequent utilization of iron in the brain. Such a decrease in iron availability could play a significant role in neuronal degeneration and increased peroxidative damage known to occur in Alzheimer's disease.
铁对正常神经功能至关重要，且在所有器官系统中受到高度调节，这一点已得到充分证实。然而，直到最近，神经系统中的铁调节才受到很少关注。本研究从尸检收集的材料中，定量比较了人类大脑三个脑皮质区域中主要铁调节蛋白、转铁蛋白和铁蛋白以及铁本身的水平。研究了三组对象：1）正常成年人（65岁以下），2）老年人（65岁以上），3）阿尔茨海默病患者。正常情况下，转铁蛋白在白质中比在灰质中更丰富。在整个检查的脑区中，铁蛋白比转铁蛋白大约丰富10倍，并且与铁一样，在灰质和白质中均匀分布。在阿尔茨海默病中，转铁蛋白持续减少，特别是在所检查的各个脑皮质区域的白质中，而铁和铁蛋白的变化则不一致。本研究中的观察结果与我们的一般假设一致，即衰老大脑中铁稳态被破坏，并且在阿尔茨海默病中铁调节蛋白的改变会加剧。转铁蛋白水平的降低可能表明大脑中铁的流动性降低以及随后的利用率降低。铁可用性的这种降低可能在阿尔茨海默病中已知发生的神经元变性和过氧化损伤增加中起重要作用。
