Department of Pediatrics, University of Minnesota, Minneapolis, MN 55455, USA.
Nutrients. 2021 Oct 28;13(11):3857. doi: 10.3390/nu13113857.
Iron deficiency (ID) anemia is the foremost micronutrient deficiency worldwide, affecting around 40% of pregnant women and young children. ID during the prenatal and early postnatal periods has a pronounced effect on neurodevelopment, resulting in long-term effects such as cognitive impairment and increased risk for neuropsychiatric disorders. Treatment of ID has been complicated as it does not always resolve the long-lasting neurodevelopmental deficits. In animal models, developmental ID results in abnormal hippocampal structure and function associated with dysregulation of genes involved in neurotransmission and synaptic plasticity. Dysregulation of these genes is a likely proximate cause of the life-long deficits that follow developmental ID. However, a direct functional link between iron and gene dysregulation has yet to be elucidated. Iron-dependent epigenetic modifications are one mechanism by which ID could alter gene expression across the lifespan. The jumonji and AT-rich interaction domain-containing (JARID) protein and the Ten-Eleven Translocation (TET) proteins are two families of iron-dependent epigenetic modifiers that play critical roles during neural development by establishing proper gene regulation during critical periods of brain development. Therefore, JARIDs and TETs can contribute to the iron-mediated epigenetic mechanisms by which early-life ID directly causes stable changes in gene regulation across the life span.
缺铁性贫血（ID）是全球首要的微量营养素缺乏症，影响约 40%的孕妇和幼儿。产前和产后早期的 ID 对神经发育有明显影响，导致认知障碍和神经精神障碍风险增加等长期影响。ID 的治疗很复杂，因为它并不总是能解决长期存在的神经发育缺陷。在动物模型中，发育性 ID 导致海马体结构和功能异常，与涉及神经递质传递和突触可塑性的基因失调有关。这些基因的失调可能是发育性 ID 后终身缺陷的直接原因。然而，铁与基因失调之间的直接功能联系尚未阐明。铁依赖性表观遗传修饰是 ID 改变整个生命周期基因表达的一种机制。 jumonji 和富含 AT 的相互作用域包含（JARID）蛋白和 Ten-Eleven Translocation（TET）蛋白是两种铁依赖性表观遗传修饰因子家族，通过在大脑发育的关键时期建立适当的基因调控，在神经发育过程中发挥关键作用。因此，JARIDs 和 TETs 可以通过铁介导的表观遗传机制，直接导致 ID 对整个寿命的基因调控产生稳定的变化。
