Engstrom Anna K, Xia Zhengui
Toxicology Program, Department of Environmental and Occupational Health Sciences, University of Washington, Seattle, WA, 98195, USA.
Neurosci Lett. 2017 Nov 20;661:108-113. doi: 10.1016/j.neulet.2017.09.060. Epub 2017 Sep 29.
Lead is a neurotoxicant of immense public health importance. Epidemiology studies suggest that heavy metal exposure may be associated with an increased risk of cognitive decline, yet few studies to date have assessed the effect of adult lead exposure on cognitive behavior in animal models. Here, we exposed 6-week-old male C57BL/6 mice to 0.2% lead acetate via drinking water for 12 weeks starting at 6 weeks of age and then assessed for deficits in hippocampus-dependent spatial memory and impairment of adult hippocampal neurogenesis. Lead did not cause locomotor deficits or anxiety in the open field test. However, we found that adult, subchronic lead exposure was sufficient to cause deficits in spatial short-term memory and these deficits persisted through at least 2 months post-lead exposure. Furthermore, we observed that lead-treated mice had fewer adult-born, mature neurons in the dentate gyrus of the hippocampus compared to control animals, suggesting that lead exposure during adolescence and adulthood may impair the neuronal differentiation of adult-born cells. These data suggest that adult lead exposure is sufficient to cause persistent deficits in spatial short-term memory and impair key processes in adult hippocampal neurogenesis.
铅是一种对公众健康具有重大意义的神经毒物。流行病学研究表明，重金属暴露可能与认知能力下降风险增加有关，但迄今为止，很少有研究评估成年期铅暴露对动物模型认知行为的影响。在此，我们从6周龄开始，让6周龄雄性C57BL/6小鼠通过饮用水接触0.2%的醋酸铅，持续12周，然后评估其海马依赖性空间记忆缺陷和成年海马神经发生受损情况。在旷场试验中，铅未导致运动功能缺陷或焦虑。然而，我们发现成年期亚慢性铅暴露足以导致空间短期记忆缺陷，且这些缺陷在铅暴露后至少持续2个月。此外，我们观察到，与对照动物相比，经铅处理的小鼠海马齿状回中成年新生的成熟神经元较少，这表明青春期和成年期的铅暴露可能会损害成年新生细胞的神经元分化。这些数据表明，成年期铅暴露足以导致空间短期记忆持续缺陷，并损害成年海马神经发生的关键过程。
