National Center for Drug Research and Evaluation, Istituto Superiore di Sanità, 00161, Rome, Italy.
Center for Behavioral Sciences and Mental Health, Istituto Superiore di Sanità, 00161, Rome, Italy.
Sci Rep. 2023 Dec 5;13(1):21448. doi: 10.1038/s41598-023-45613-2.
Micronutrients such as selenium (Se) are essentials since prenatal life to support brain and cognitive development. Se deficiency, which affects up to 1 billion people worldwide, can interact with common adverse environmental challenges including (Pb), exacerbating their toxic effects. Exploiting our recently validated rat model of maternal Se restriction and developmental low Pb exposure, our aims were to investigate: (i) the early consequences of suboptimal Se intake and low-Pb exposure on neuroinflammation in neonates' whole brains; (ii) the potential priming effect of suboptimal Se and low-Pb exposure on offspring's glial reactivity to a further inflammatory hit. To these aims female rats were fed with suboptimal (0.04 mg/kg; Subopt) and optimal (0.15 mg/kg; Opt) Se dietary levels throughout pregnancy and lactation and exposed or not to environmentally relevant Pb dose in drinking water (12.5 µg/mL) since 4 weeks pre-mating. We found an overall higher basal expression of inflammatory markers in neonatal brains, as well as in purified microglia and organotypic hippocampal slice cultures, from the Subopt Se offspring. Subopt/Pb cultures were highly activated than Subopt cultures and showed a higher susceptibility to the inflammatory challenge lipopolysaccharide than cultures from the Opt groups. We demonstrate that even a mild Se deficiency and low-Pb exposure during brain development can influence the neuroinflammatory tone of microglia, exacerbate the toxic effects of Pb and prime microglial reactivity to subsequent inflammatory stimuli. These neuroinflammatory changes may be responsible, at least in part, for adverse neurodevelopmental outcomes.
微量营养素，如硒（Se），是从胎儿期开始支持大脑和认知发育所必需的。全球有多达 10 亿人受到硒缺乏的影响，而这种情况可能与常见的环境挑战因素（如铅（Pb））相互作用，加剧其毒性作用。利用我们最近验证的母体硒限制和发育性低 Pb 暴露大鼠模型，我们的目的是研究：（i）亚硒酸钠摄入不足和低 Pb 暴露对新生儿全脑神经炎症的早期影响；（ii）亚硒酸钠和低 Pb 暴露对子代对进一步炎症打击的神经胶质反应的潜在启动效应。为此，雌性大鼠在整个怀孕期间和哺乳期都以亚硒酸钠（0.04mg/kg；Subopt）和最佳（0.15mg/kg；Opt）硒饮食水平喂养，并从交配前 4 周开始在饮用水中暴露于或不暴露于环境相关的 Pb 剂量（12.5μg/ml）。我们发现，来自亚硒酸钠（Subopt）后代的新生儿大脑以及纯化的小胶质细胞和器官型海马切片培养物中，炎症标志物的总体基础表达水平更高。Subopt/Pb 培养物比 Subopt 培养物更高度激活，并且对炎症挑战脂多糖的敏感性高于来自 Opt 组的培养物。我们证明，即使在大脑发育过程中存在轻度的硒缺乏和低 Pb 暴露，也会影响小胶质细胞的神经炎症状态，加剧 Pb 的毒性作用，并使小胶质细胞对随后的炎症刺激产生反应。这些神经炎症变化可能至少部分导致不良的神经发育结局。
