Centre for Behavioral Sciences and Mental Health, Istituto Superiore di Sanità (ISS), 00161 Rome, Italy.
Department of Pharmacological and Biomolecular Sciences, Università degli Studi di Milano, 20133 Milan, Italy.
Int J Mol Sci. 2020 Apr 11;21(8):2664. doi: 10.3390/ijms21082664.
Lead (Pb) exposure in early life affects brain development resulting in cognitive and behavioral deficits. Epidemiologic and experimental evidence of sex as an effect modifier of developmental Pb exposure is emerging. In the present study, we investigated Pb effects on behavior and mechanisms of neuroplasticity in the hippocampus and potential sex differences. To this aim, dams were exposed, from one month pre-mating to offspring weaning, to Pb via drinking water at 5 mg/kg body weight per day. In the offspring of both sexes, the longitudinal assessment of motor, emotional, and cognitive end points was performed. We also evaluated the expression and synaptic distribution of N-methyl-D-Aspartate receptor (NMDA) and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor subunits at post-natal day (pnd) 23 and 70 in the hippocampus. Neonatal motor patterns and explorative behavior in offspring were affected in both sexes. Pb effects in emotional response and memory retention were observed in adult females only, preceded by increased levels of GluN2A and GluA1 subunits at the post-synapse at pnd 23. These data suggest that Pb exposure during development affects glutamatergic receptors distribution at the post-synaptic spine in females. These effects may contribute to alterations in selected behavioral domains.
铅（Pb）暴露在生命早期会影响大脑发育，导致认知和行为缺陷。越来越多的流行病学和实验证据表明，性别是发育性 Pb 暴露的效应修饰因子。在本研究中，我们研究了 Pb 对行为和海马体神经可塑性机制的影响，以及潜在的性别差异。为此，从受孕前一个月到幼崽断奶，母鼠通过饮用水每天摄入 5mg/kg 体重的 Pb。在雌雄后代中，均进行了运动、情绪和认知终点的纵向评估。我们还评估了海马体中 N-甲基-D-天冬氨酸受体（NMDA）和 α-氨基-3-羟基-5-甲基-4-异恶唑丙酸（AMPA）受体亚基在出生后第 23 天和第 70 天的表达和突触分布。在雌雄后代中，新生儿的运动模式和探索行为都受到影响。只有成年雌性出现了情绪反应和记忆保留方面的 Pb 效应，这之前是突触后 GluN2A 和 GluA1 亚基水平升高。这些数据表明，发育过程中的 Pb 暴露会影响雌性突触后棘突上的谷氨酸能受体分布。这些影响可能导致特定行为领域的改变。
