Oligodendrocyte generation during iron deficiency

描述（由申请人提供）：世界上最普遍的营养素缺乏症是缺铁。据估计，35%至58%的妇女有一定程度的缺铁。铁缺乏症的发生在怀孕期间特别普遍。据报道，对于2岁以下的儿童，估计缺铁的患病率为25%。虽然已知儿童缺铁与许多神经缺陷相关，包括行为影响、血脑屏障改变、脂肪酸组成变化和髓鞘形成不足，但导致此类缺陷的细胞机制尚未完全了解。例如，已经假设缺铁导致少突胶质细胞成熟或存活的失败。另一个已经讨论过的可能性是，由于缺铁，少突胶质细胞不能从产生少突胶质细胞的前体细胞产生。这些假设是基于观察，有一个峰值的铁在体内的可用性，正好与髓鞘形成的高峰期，正常的髓鞘形成不会发生在没有足够的铁。 绝大多数试图破译铁在胶质细胞生成中的特定作用的研究都集中在出生后的发育阶段，此时少突胶质细胞在体内形成功能性髓鞘。然而，我们自己的研究表明，缺铁对胚胎脊髓的早期胶质前体细胞有严重影响。 在低铁环境中生长的胚胎神经胶质前体细胞分裂和分化的能力似乎受损。因此，我们现在提出，与缺铁相关的髓鞘形成不足可能是胚胎发生过程中已经发生的损伤的晚期后果。我们认为铁干扰了少突胶质细胞生成的最早期发育步骤，因此破坏了这些髓鞘生成细胞正常生成所需的正常进行性谱系限制序列。

DESCRIPTION (provided by applicant): The most prevalent nutrient deficiency in the world is a lack of iron. It has been estimated that 35 to 58% of women have some degree of iron deficiency. The occurrence of iron deficiency is particularly prevalent during pregnancy. It has been reported that for children under 2 years of age, the estimated prevalence of iron deficiency is 25%. While it is known that iron deficiency in children is associated with a number of neural defects including behavioral effects, alterations to the blood brain barrier, changes in fatty acid composition, and hypo-myelination, the cellular mechanisms leading to such defects are not well understood. For example, it has been hypothesized that iron deficiency leads to a failure of oligodendrocyte maturation or survival. Another possibility that has been discussed is a failure in the generation of oligodendrocytes from the precursor cells that give rise to them due to iron deficiency. These hypotheses are based on observations that there is a peak of iron availability in vivo that coincides precisely with peak periods of myelination and that normal myelination does not occur in the absence of sufficient iron. The vast majority of studies that try to decipher the specific role of iron in gliogenesis have focused on the postnatal stage of development, when oligodendrocytes form functional myelin in vivo. Our own studies, however, have indicated that a lack of iron has a severe impact on the very early glial precursor cells of the embryonic spinal cord. Embryonic glial precursor cells that grow in low iron seem to be impaired in their ability to divide and to differentiate. Thus, we now propose that the hypomyelination that is associated with iron deficiency is likely to be a late consequence of damage that occurred already during embryogenesis. We propose that iron interferes with the earliest developmental steps ancestral to oligodendrocyte generation and therefore disrupts the normal sequence of progressive lineage restriction that is required for proper generation of these myelin-producing cells.