Dubrof Stephanie, Zukaitis Jillien G, Ahmed Ishfaque, Sun Wenwu, Zhao Qun, Park Hea Jin
Department of Nutritional Sciences, University of Georgia, Athens, United States.
Department of Physics and Astronomy, University of Georgia, Athens, United States.
Biochim Biophys Acta Mol Cell Biol Lipids. 2025 Jun;1870(5):159629. doi: 10.1016/j.bbalip.2025.159629. Epub 2025 May 13.
The perinatal period is crucial for fetal neurological development, relying on omega-3 polyunsaturated fatty acids (PUFAs) for essential processes. Omega-3 PUFA, including docosahexaenoic acid (DHA), are precursors to a novel class of bioactive metabolites called specialized pro-resolving mediators (SPMs), which have been suggested to have a dual purpose in mitigating neuroinflammation while simultaneously supporting cognitive outcomes, implicating a role in offspring neurodevelopment. DHA is evidenced for its role in early brain development, but the underlying mechanism it exerts its cognitive benefits remain unclear. Pregnant sows were fed a control diet (CON; n = 6) or a diet with DHA (n = 6, 75 mg DHA/kg BW/day) from gestation through lactation. At weaning, piglets (n = 2/sow) underwent resting state-functional magnetic resonance imaging (rs-fMRI) to assess brain functional activation. Subsequently, brain tissue from prefrontal cortex, cerebellum, and hippocampus were collected from piglets. Tissue DHA and eicosapentaenoic acid (EPA)-derived SPMs were quantified using LC-MS. Levels of SPMs were higher in the brains of piglets from DHA-fed sows, particularly in the prefrontal cortex and cerebellum, compared to control piglets. Additionally, a distinct association of several prefrontal SPMs with activation of the cerebellar functional network was marked in the piglet offspring. The findings highlight a potential for SPMs to function as mediators for neurodevelopmental programming, through contributing to inflammation resolution and neuronal connectivity. This work underscores the importance of maternal nutrition in shaping offspring brain health and lays the groundwork for targeted interventions leveraging the benefits of DHA and its bioactive metabolites.
围产期对胎儿神经发育至关重要，胎儿的关键发育过程依赖于ω-3多不饱和脂肪酸（PUFA）。ω-3多不饱和脂肪酸，包括二十二碳六烯酸（DHA），是一类名为特殊促消退介质（SPM）的新型生物活性代谢物的前体，有人认为这些介质在减轻神经炎症的同时支持认知结果方面具有双重作用，这表明其在后代神经发育中发挥作用。DHA在早期大脑发育中的作用已有证据，但它发挥认知益处的潜在机制仍不清楚。从妊娠到哺乳期间，给怀孕母猪喂食对照日粮（CON；n = 6）或含DHA的日粮（n = 6，75毫克DHA/千克体重/天）。断奶时，对仔猪（每头母猪2头仔猪）进行静息态功能磁共振成像（rs-fMRI）以评估脑功能激活情况。随后收集仔猪前额叶皮质、小脑和海马体的脑组织。使用液相色谱-质谱联用技术对组织中的DHA和二十碳五烯酸（EPA）衍生的SPM进行定量。与对照仔猪相比，喂食DHA的母猪所产仔猪大脑中SPM水平更高，尤其是在前额叶皮质和小脑中。此外，在仔猪后代中发现几种前额叶SPM与小脑功能网络的激活存在明显关联。这些发现突出了SPM作为神经发育编程介质的潜力，通过促进炎症消退和神经元连接发挥作用。这项工作强调了母体营养对塑造后代大脑健康的重要性，并为利用DHA及其生物活性代谢物的益处进行有针对性的干预奠定了基础。
