Isac Sebastian, Panaitescu Anca Maria, Iesanu Mara, Grigoras Ioana Florentina, Totan Alexandra, Udriste Amalia, Cucu Natalia, Peltecu Gheorghe, Zagrean Leon, Zagrean Ana-Maria
Division of Physiology and Neuroscience, Carol Davila University of Medicine and Pharmacy, Bucharest, Romania.
Filantropia Clinical Hospital, Bucharest, Romania.
Neonatology. 2018;114(4):355-361. doi: 10.1159/000491383. Epub 2018 Aug 22.
High-fat diet (HFD) is a detrimental habit with harmful systemic consequences, including low-grade, long-lasting inflammation. During pregnancy, HFD can induce developmental changes. Moreover, HFD-related maternal obesity might enhance the risk of peripartum complications including hypoxic-ischemic encephalopathy secondary to perinatal asphyxia (PA).
Following our previous results showing that PA increases neuroinflammation and neuronal injury in the immature hippocampus and modifies hippocampal epigenetic programming, we further aimed to establish the impact of maternal HFD on offspring hippocampus response to PA.
We assessed hippocampal tumor necrosis factor alpha (TNFα), interleukin 1 beta -(IL-1b) and S-100B protein (S-100B), 24-48 h after PA exposure in postnatal day 6 Wistar rats, whose mothers received either the standard diet or HFD. The expression of small non-coding microRNA species miR124, miR132, miR134, miR146, and miR15a, as epigenetic markers for the maternal dietary influence on immature hippocampus response after PA, was determined 24 h after asphyxia exposure. Metabolic activity was measured using resazurin test in hippocampal cell suspension obtained 24 h after PA.
Our results indicate that maternal HFD additionally increases hippocampal TNFα, IL-1b, and S-100B after PA. Also, PA associated with maternal HFD induces miR124 upregulation and miR132 downregulation relative to PA only. Metabolic activity was increased in hippocampal cells from pups whose mothers received HFD.
HFD increases the PA-induced neuroinflammation and neuronal injury, and epigenetically influences homeostatic synaptic plasticity and neuronal tolerance to asphyxia, processes associated with a higher hippocampal cellular metabolism.
高脂饮食（HFD）是一种有害习惯，会产生有害的全身影响，包括低度、持续的炎症。在孕期，高脂饮食会引发发育变化。此外，与高脂饮食相关的母体肥胖可能会增加围产期并发症的风险，包括围产期窒息（PA）继发的缺氧缺血性脑病。
基于我们之前的研究结果，即围产期窒息会增加未成熟海马体中的神经炎症和神经元损伤，并改变海马体的表观遗传编程，我们进一步旨在确定母体高脂饮食对后代海马体对围产期窒息反应的影响。
我们评估了出生后第6天的Wistar大鼠海马体中肿瘤坏死因子α（TNFα）、白细胞介素1β（IL-1b）和S-100B蛋白（S-100B）的水平，这些大鼠的母亲在孕期分别接受标准饮食或高脂饮食，在围产期窒息暴露后24 - 48小时进行评估。作为母体饮食对围产期窒息后未成熟海马体反应影响的表观遗传标志物，在窒息暴露后24小时测定小非编码微小RNA种类miR124、miR132、miR134、miR146和miR15a的表达。使用刃天青试验在围产期窒息后24小时获得的海马体细胞悬液中测量代谢活性。
我们的结果表明，母体高脂饮食会在围产期窒息后进一步增加海马体中的TNFα、IL-1b和S-100B。此外，与母体高脂饮食相关的围产期窒息相对于单纯围产期窒息会诱导miR124上调和miR132下调。母亲接受高脂饮食的幼崽海马体细胞中的代谢活性增加。
高脂饮食会增加围产期窒息诱导的神经炎症和神经元损伤，并在表观遗传上影响稳态突触可塑性和神经元对窒息的耐受性，这些过程与较高的海马体细胞代谢有关。
