Connor J R
Department of Neuroscience and Anatomy, Pennsylvania State University School of Medicine, M.S. Hershey Medical Center, Hershey 17033, USA.
Dev Neurosci. 1994;16(5-6):233-47. doi: 10.1159/000112115.
The World Health Organization considers iron deficiency the number one nutritional disorder in the world. In this review, the normal pattern for iron accumulation and expression of iron regulatory proteins (transferrin and its receptor, and ferritin) in brain during development are examined biochemically and at the cellular and molecular levels. Iron and the iron-regulatory proteins are at their highest postnatal concentration in the brain at birth, decline over the preweaning period and then increase to adult levels. Evidence is presented that in utero exposure to alcohol, iron-deficient diets, and dysfunctional oligodendrocytes can influence the normal pattern for iron accumulation in the brain which sets off a cascade of events that results in loss of regulatory control of iron. Because iron is an essential cofactor in neurotransmitter synthesis and myelination altering iron availability during vulnerable periods of development may have a permanent influence both on iron homeostasis in the brain and motor and cognitive function. At the cellular level, iron-positive cells in the subventricular zone and myelinogenic foci are present as early as postnatal day 3. Disruption of oligodendrocyte maturation is associated with altered expression and cellular accumulation of iron, transferrin and the transferrin receptor in brain. These data indicate that iron delivered via transferrin and its receptor is intrinsically involved in oligodendrocyte maturation and thus plays a critical role in the onset of myelination. In the adult, oligodendrocytes are the predominant iron-regulatory cell in the brain by virtue of their high content of iron, transferrin and ferritin. From these studies we conclude oligodendrocytes may be responsible for iron regulation in the brain at the cellular level and that brain iron regulatory mechanisms are vulnerable to manipulation during postnatal development.
世界卫生组织认为缺铁是全球头号营养失调问题。在本综述中，从生化以及细胞和分子水平研究了大脑在发育过程中铁积累的正常模式以及铁调节蛋白（转铁蛋白及其受体和铁蛋白）的表达情况。铁和铁调节蛋白在出生时大脑中的浓度为出生后最高，在断奶前期下降，然后增加至成年水平。有证据表明，子宫内暴露于酒精、缺铁饮食以及少突胶质细胞功能失调会影响大脑中铁积累的正常模式，进而引发一系列事件，导致铁的调节控制丧失。由于铁是神经递质合成和髓鞘形成过程中必不可少的辅助因子，在发育的脆弱阶段改变铁的可利用性可能会对大脑中的铁稳态以及运动和认知功能产生永久性影响。在细胞水平上，早在出生后第3天，脑室下区和髓鞘形成灶中就存在铁阳性细胞。少突胶质细胞成熟的破坏与大脑中铁、转铁蛋白和转铁蛋白受体的表达改变及细胞内积累有关。这些数据表明，通过转铁蛋白及其受体传递的铁本质上参与了少突胶质细胞的成熟，因此在髓鞘形成的起始过程中起关键作用。在成人大脑中，少突胶质细胞凭借其高含量的铁、转铁蛋白和铁蛋白，成为主要的铁调节细胞。从这些研究中我们得出结论，少突胶质细胞可能在细胞水平上负责大脑中的铁调节，并且大脑铁调节机制在出生后发育过程中容易受到影响。
