Lead (Pb) is recognized as a potent inducer of synaptic toxicity generally associated with reduced synaptic transmission and increased neuronal fiber excitability, becoming an environmental risk for neurodegenerative processes. Despite numerous toxicological studies on Pb have been directed to the developing brain, attention concerning long-term consequences of pubertal chronic Pb exposure on neuronal activity is still lacking. Thus, we exposed 4-week-old male mice to 0.2 % lead acetate solution for one month, then, conducted behavioral tests or extracted brain homogenate from mice prefrontal cortex (PFC) and hippocampus at the age of 4, 13 and 16-month-old respectively. Our results showed that treated mice exhibited an evident increase in latency to reach platform following pubertal Pb exposure and aging. The increase of 8-OHdG revealed evident neural DNA oxidative damage across time upon pubertal Pb exposure. In the hippocampus of lead exposed mice at three age nodes, the expression of brain-derived neurotrophic factor precursor (proBDNF) increased, while that of mature BDNF (mBDNF), cAMP-response element binding protein (CREB) and phosphorylated CREB (pCREB) decreased compared with the control group. Furthermore, the expression of BACE1 protein and tau phosphorylation level in PFC and hippocampus increased, APP mRNAs in PFC and prolonged induction of BACE1 in hippocampus. Our results show that chronic Pb exposure from pubertal stage onward can either initiate divergent synaptic-related gene expression patterns in adulthood or trigger time-course of neurodegenerative profile within the PFC or hippocampus, which can contribute consistent deficits of cognition across subsequent age-nodes.

铅（Pb）被认为是有效的突触毒性诱导剂，通常与减少的突触传递和增加的神经元纤维兴奋性有关，成为神经变性过程的环境风险。尽管对铅的发育进行了大量毒理学研究，但仍缺乏对青春期慢性铅暴露对神经元活动的长期后果的关注。因此，我们将4周龄的雄性小鼠暴露于0.2％乙酸铅溶液中一个月，然后进行行为测试或从4、13和16个月大的小鼠前额叶皮层（PFC）和海马中提取脑匀浆-分别。我们的结果表明，经过治疗的小鼠在青春期Pb暴露和衰老后，到达平台的潜伏期明显增加。暴露于青春期铅后，8-OHdG的增加揭示了明显的神经DNA氧化损伤。在三个年龄节点的铅暴露小鼠海马中，脑源性神经营养因子前体（proBDNF）的表达增加，而成熟BDNF（mBDNF），cAMP反应元件结合蛋白（CREB）和磷酸化CREB（pCREB）的表达增加。与对照组相比下降。此外，PFC和海马中BACE1蛋白的表达和tau磷酸化水平增加，PFC中的APP mRNA表达增加，海马中BACE1的诱导时间延长。我们的研究结果表明，从青春期开始长期接触铅可能会引发成年后不同的突触相关基因表达模式，或者触发PFC或海马内神经退行性反应的时程，