Department of Public Health Sciences, College of Health Sciences, University of Texas, El Paso, USA.
Toxicol Lett. 2013 Jun 20;220(1):44-52. doi: 10.1016/j.toxlet.2013.04.003. Epub 2013 Apr 15.
The mechanisms by which early chronic lead (Pb) exposure alter brain development have not been identified. We examined neuroimmune system effects in C57BL/6J mice with Pb exposure, including levels that may be common among children in lower socioeconomic income environments. Pups were exposed via dams' drinking water from birth to post-natal day 28 to low, high or no Pb conditions. We compared gene expression of neuroinflammatory markers (study 1); and microglial mean cell body volume and mean cell body number in dentate gyrus, and dentate gyrus volume (study 2). Blood Pb levels in exposed animals at sacrifice (post-natal day 28) ranged from 2.66 to 20.31μg/dL. Only interleukin-6 (IL6) differed between groups and reductions were dose-dependent. Microglia cell body number also differed between groups and reductions were dose-dependent. As compared with controls, microglia cell body volume was greater but highly variable in only low-dose animals; dentate gyri volumes in low- and high-dose animals were reduced. The results did not support a model of increased neuroinflammation. Instead, early chronic exposure to Pb disrupted microglia via damage to, loss of, or lack of proliferation of microglia in the developing brains of Pb-exposed animals.
早期慢性铅（Pb）暴露改变大脑发育的机制尚未确定。我们研究了 C57BL/6J 小鼠在 Pb 暴露下的神经免疫系统效应，包括可能在低收入环境中儿童中常见的水平。从出生到出生后 28 天，幼崽通过母鼠饮用水暴露于低、高或无 Pb 条件下。我们比较了神经炎症标志物的基因表达（研究 1）；以及齿状回的小胶质细胞平均细胞体体积和平均细胞体数量，以及齿状回体积（研究 2）。暴露动物在牺牲时（出生后 28 天）的血液 Pb 水平在 2.66 至 20.31μg/dL 之间。只有白细胞介素 6（IL6）在组间存在差异，且减少呈剂量依赖性。小胶质细胞体数量也在组间存在差异，且减少呈剂量依赖性。与对照组相比，只有低剂量组的小胶质细胞体体积更大，但变化很大；低剂量和高剂量组的齿状回体积减小。结果不支持神经炎症增加的模型。相反，早期慢性 Pb 暴露通过损害、丧失或缺乏 Pb 暴露动物发育中大脑的小胶质细胞增殖，破坏了小胶质细胞。
