Department of Pediatrics, University of Minnesota, Minneapolis, MN, United States.
Research Informatic Solutions, Minnesota Supercomputing Institute, University of Minnesota, Minneapolis, MN, United States.
J Nutr. 2024 Apr;154(4):1141-1152. doi: 10.1016/j.tjnut.2024.02.021. Epub 2024 Feb 24.
Developmental iron deficiency (ID) is associated with long-term cognitive and affective behavioral impairments in humans. Preclinical studies have shown that developmental ID has short- and long-term effects on gene regulation. Prenatal choline supplementation partially rescues early-life ID-induced cognitive deficits in adult male rats.
To identify acute and long-term changes in biological processes regulated by developmental ID and modifiable by choline.
This study compares the hippocampal transcriptomes of postnatal day (P) 15 iron-deficient (acute) and P65 formerly ID (persistent) rats with or without prenatal choline treatment. Pregnant rats were fed an ID (4 mg/kg Fe) or iron-sufficient (IS) (200 mg/kg Fe) diet from gestational day (G) 2 to P7 with or without choline supplementation (5 g/kg choline) from G11 to G18. Hippocampi were collected from P15 or P65 offspring and analyzed for gene expression by RNA sequencing.
Developmental ID-induced changes suggested modified activity of oxidative phosphorylation and fatty acid metabolism. Prenatal choline supplementation induced robust changes in gene expression, particularly in iron-deficient animals, where it partially mitigated the early-life ID-dysregulated genes. Choline supplementation also altered the hippocampal transcriptome in the IS rats, with indications for both beneficial and adverse effects.
This study provided global assessments of gene expression regulated by iron and choline. Our new findings highlight genes responding to iron or choline treatments, including a potentially novel choline-regulated transporter (IPO7), with shared effects on neuroinflammation in the male rat hippocampus.
发育性铁缺乏(ID)与人类的长期认知和情感行为障碍有关。临床前研究表明,发育性 ID 对基因调控有短期和长期影响。产前胆碱补充部分挽救了成年雄性大鼠生命早期 ID 诱导的认知缺陷。
确定由发育性 ID 调节的生物学过程的急性和长期变化,并确定胆碱可调节的变化。
本研究比较了产后第 15 天(P)铁缺乏(急性)和 P65 前 ID(持续)大鼠的海马转录组,以及是否有产前胆碱处理。从妊娠第 2 天(G)到 P7,怀孕的大鼠分别用 ID(4 mg/kg Fe)或铁充足(IS)(200 mg/kg Fe)饮食喂养,从 G11 到 G18 用或不用胆碱补充(5 g/kg 胆碱)。从 P15 或 P65 后代中收集海马体,并通过 RNA 测序分析基因表达。
发育性 ID 诱导的变化表明氧化磷酸化和脂肪酸代谢的活性发生了改变。产前胆碱补充诱导了基因表达的强烈变化,特别是在铁缺乏的动物中,部分缓解了生命早期 ID 失调的基因。胆碱补充也改变了 IS 大鼠的海马转录组,显示出有益和不利的影响。
本研究对铁和胆碱调节的基因表达进行了全面评估。我们的新发现强调了对铁或胆碱处理有反应的基因,包括一个潜在的新型胆碱调节转运体(IPO7),它对雄性大鼠海马体的神经炎症有共同的影响。