CSF proteomic analysis reveals persistent iron deficiency-induced alterations in non-human primate infants
CSF proteomic analysis reveals persistent iron deficiency-induced alterations in non-human primate infants
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DOI：
10.1111/j.1471-4159.2007.05113.x
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发表时间：
2008-04-01
影响因子：
4.7
通讯作者：
Connor, James R.
中科院分区：
文献类型：
--
作者：
Geguchadze, Ramaz N.;Coe, Christopher L.;Connor, James R.
婴儿期缺铁（ID）贫血会导致长期的神经系统后果，但其介导机制仍不清楚。幼猴通常在生命的前 6 个月内自然贫血，这为确定发育性缺铁的影响提供了机会。断奶后，随机选择动物补充口服铁或饲喂标准商业饲料。对照组从未缺铁。血液学参数显示，两组贫血均在 12 个月后得到纠正。在 12 个月大时收集脑脊液进行蛋白质组分析，以评估发育性 ID 对大脑的影响。两个先前缺铁组的脑脊液蛋白质组相似，并显示 12 种蛋白质的表达水平至少改变了一倍。这些蛋白质通过基质辅助激光解吸电离飞行时间光谱法进行鉴定，包括前列腺素 D 合酶、嗅觉受体和神经胶质纤维酸性蛋白。因此，蛋白质组分析揭示了智力障碍的持续影响，并为睡眠障碍、髓鞘形成不足和其他与智力障碍相关的行为改变的报告提供了见解。此外，尽管血液学参数正常，但脑脊液蛋白质组的变化表明存在一个分层系统，优先考虑补充红细胞团，而牺牲大脑。
Iron deficiency (ID) anemia during infancy results in long-term neurological consequences, yet the mediating mechanisms remain unclear. Infant monkeys often become naturally anemic during the first 6 months of life, presenting an opportunity to determine the effect of developmental iron deficiency. After weaning, animals were chosen randomly for supplementation with oral iron or, fed a standard commercial chow diet. The control group was never iron deficient. ID anemia was corrected by 12 months in both groups, as indicated by hematological parameters. CSF was collected for proteomic analysis at 12 months of age to assess the impact of developmental ID on the brain. The CSF proteome for both formerly iron deficient groups was similar and revealed 12 proteins with expression levels altered at least twofold. These proteins were identified by matrix assisted laser desorption ionization time-of-flight spectrometry and included prostaglandin D synthase, olfactory receptors and glial fibrillary acidic protein. Thus the proteomic analysis reveals a persistent effect of ID and provides insights into reports of disturbed sleep, hypomyelination and other behavioral alterations associated with ID. Furthermore, alterations in the CSF proteome despite normal hematologic parameters indicate that there is a hierarchical system that prioritizes repletion of red cell mass at the expense of the brain.