Ouyang Lu, Li Qi, Rao Shaoqi, Su Rui, Zhu Yanhui, Du Guihua, Xie Jie, Zhou Fankun, Feng Chang, Fan Guangqin
School of Public Health, Nanchang University, Nanchang, 330006, PR China; State Key Laboratory of Food Science and Technology, Nanchang University, Nanchang, 330047, PR China.
School of Public Health, Nanchang University, Nanchang, 330006, PR China.
Food Chem Toxicol. 2023 May;175:113707. doi: 10.1016/j.fct.2023.113707. Epub 2023 Mar 7.
Contaminated water and food are the main sources of lead, cadmium, and mercury in the human body. Long-term and low-level ingestion of these toxic heavy metals may affect brain development and cognition. However, the neurotoxic effects of exposure to lead, cadmium, and mercury mixture (Pb + Cd + Hg) at different stages of brain development are rarely elucidated. In this study, different doses of low-level Pb + Cd + Hg were administered to Sprague-Dawley rats via drinking water during the critical stage of brain development, late stage, and after maturation, respectively. Our findings showed that Pb + Cd + Hg exposure decreased the density of memory- and learning-related dendritic spines in the hippocampus during the critical period of brain development, resulting in hippocampus-dependent spatial memory deficits. Only the density of learning-related dendritic spines was reduced during the late phase of brain development and a higher-dose of Pb + Cd + Hg exposure was required, which led to hippocampus-independent spatial memory abnormalities. Exposure to Pb + Cd + Hg after brain maturation revealed no significant change in dendritic spines or cognitive function. Further molecular analysis indicated that morphological and functional changes caused by Pb + Cd + Hg exposure during the critical phase were associated with PSD95 and GluA1 dysregulation. Collectively, the effects of Pb + Cd + Hg on cognition varied depending on the brain development stages.
受污染的水和食物是人体中铅、镉和汞的主要来源。长期低剂量摄入这些有毒重金属可能会影响大脑发育和认知能力。然而，在大脑发育的不同阶段，接触铅、镉和汞混合物（Pb + Cd + Hg）的神经毒性作用鲜有阐明。在本研究中，分别在大脑发育的关键期、晚期和成熟后，通过饮用水给斯普拉格-道利大鼠施用不同剂量的低水平Pb + Cd + Hg。我们的研究结果表明，在大脑发育的关键期，接触Pb + Cd + Hg会降低海马体中与记忆和学习相关的树突棘密度，导致依赖海马体的空间记忆缺陷。在大脑发育后期，仅与学习相关的树突棘密度降低，且需要更高剂量的Pb + Cd + Hg暴露，这导致不依赖海马体的空间记忆异常。大脑成熟后接触Pb + Cd + Hg，树突棘或认知功能未显示出显著变化。进一步的分子分析表明，在关键期，Pb + Cd + Hg暴露引起的形态和功能变化与PSD95和GluA1失调有关。总的来说，Pb + Cd + Hg对认知的影响因大脑发育阶段而异。
