Dept of Public Health Sciences, University of Texas, El Paso, TX, United States; Border Biomedical Research Center, Toxicology Core, University of Texas, El Paso, TX, United States.
Border Biomedical Research Center, Toxicology Core, University of Texas, El Paso, TX, United States; Dept of Psychology, University of Texas, El Paso, TX, United States.
Toxicol Lett. 2019 Mar 1;302:75-82. doi: 10.1016/j.toxlet.2018.10.016. Epub 2018 Oct 21.
Developmental lead (Pb) exposure alters brain function through mechanisms that are not yet understood. A previous study showed that early lead exposure reduced microglia number in the dentate gyrus region of the hippocampus. Given the critical role of microglia in brain development, it is important to determine whether these differences are unique to the dentate gyrus, or occur throughout the hippocampus. Unbiased stereology was used to quantify microglia mean cell body number in total hippocampus, and compare the proportion of microglia in the ventral vs. dorsal regions. Total hippocampal volume was also measured and compared. The study included brain tissue from 30 pre-adolescent C57BL/6 J mice, exposed to 30 ppm Pb acetate (n = 10, mean BLL 3.4 μg/dL at sacrifice), 330 ppm Pb acetate (n = 10, mean BLL 14.1 μg/dL at sacrifice), or 0 ppm Pb acetate (n = 10, negative controls). In lead exposed animals, microglia mean cell body number was reduced in total hippocampus; total hippocampal volume was reduced. Importantly, effects in low- and high-dose exposure groups did not differ. Contrary to study hypotheses, the distribution of hippocampal microglia in the ventral vs. dorsal hippocampal regions did not differ. Overall, lowest and higher levels of lead exposure during development had strikingly similar disruptive effects in the neuroimmune system. Studies are needed to determine the immune and other mechanisms responsible for these effects. Future studies would benefit from larger samples to determine whether in fact there is a group by sex interaction driving the effects of early lead exposure on microglia.
发育性铅（Pb）暴露通过尚未完全了解的机制改变大脑功能。先前的研究表明，早期铅暴露会减少海马齿状回区的小胶质细胞数量。鉴于小胶质细胞在大脑发育中的关键作用，重要的是要确定这些差异是否仅存在于齿状回区，还是整个海马区都存在。采用无偏立体学方法定量分析总海马中小胶质细胞的平均细胞体数量，并比较腹侧与背侧区域中小胶质细胞的比例。还测量和比较了总海马体积。该研究包括 30 只青春期前 C57BL/6J 小鼠的脑组织，这些小鼠暴露于 30ppm 的醋酸铅（n=10，牺牲时平均 BLL 为 3.4μg/dL）、330ppm 的醋酸铅（n=10，牺牲时平均 BLL 为 14.1μg/dL）或 0ppm 的醋酸铅（n=10，阴性对照）。在铅暴露动物中，总海马中小胶质细胞的平均细胞体数量减少；总海马体积减少。重要的是，低剂量和高剂量暴露组的影响没有差异。与研究假设相反，腹侧和背侧海马区的海马小胶质细胞分布没有差异。总的来说，在发育过程中最低和最高水平的铅暴露对神经免疫系统具有惊人相似的破坏性影响。需要研究确定这些影响所涉及的免疫和其他机制。未来的研究需要更大的样本量来确定早期铅暴露对小胶质细胞的影响是否实际上存在性别交互作用的群体。
