Background

Exposures to lead (Pb) during developmental phases can alter the normal course of development, with lifelong health consequences. Permanent Pb exposure leads to behavioral changes, cognitive impairment, sympathoexcitation, tachycardia, hypertension and autonomic dysfunction. However, the effects of an intermittent lead exposure are not yet studied. This pattern of exposure has been recently increasing due to migrations, implementation of school exchange programs and/or residential changes.

Objective

To determine and compare lead effects on mammal’s behavior and physiology, using a rat model of intermittent and permanent Pb exposures.

Methods

Fetuses were intermittently (PbI) or permanently (PbP) exposed to water containing lead acetate (0.2% w/v) throughout life until adulthood (28 weeks of age). A control group (CTL) without any exposure to lead was also used.

Anxiety was assessed by elevated plus maze (EPM) and locomotor activity and exploration by open field test (OFT). Blood pressure (BP), electrocardiogram (ECG), heart rate (HR), respiratory frequency (RF), sympathetic and parasympathetic activity and baro- and chemoreceptor reflex profiles were evaluated. Immunohistochemistry protocol for the assessment of neuroinflammation, neuronal loss (NeuN), gliosis and synaptic alterations (Iba-1, GFAP, Syn), were performed at the hippocampus. One-way ANOVA with Tukey’s multiple comparison between means were used (significance p < 0.05) for statistical analysis.

Results

The intermittent lead exposure produced a significant increase in diastolic and mean BP values, concomitant with a tendency to sympathetic overactivity (estimated by increased low-frequency power) and without significant changes in systolic BP, HR and RF. A chemoreceptor hypersensitivity and a baroreflex impairment were also observed, however, less pronounced when compared to the permanent exposure. Regarding behavioral changes, both lead exposure profiles showed an anxiety-like behavior without changes in locomotor and exploratory activity. Increase in GFAP and Iba-1 positive cells, without changes in NeuN positive cells were found in both exposed groups. Syn staining suffered a significant decrease in PbI group and a significant increase in PbP group.

Conclusion

This study is the first to show that developmental Pb exposure since fetal period can cause lasting impairments in physiological parameters. The intermittent lead exposure causes adverse health effects, i.e, hypertension, increased respiratory frequency and chemoreflex sensitivity, baroreflex impairment, anxiety, decreased synaptic activity, neuroinflammation and reactive gliosis, in some ways similar to a permanent exposure, however some are lower-grade, due to the shorter duration of exposure.

This study brings new insights on the environmental factors that influence autonomic and cardiovascular systems during development, which can help in creating public policy strategies to prevent and control the adverse effects of Pb toxicity.

中文翻译：

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间歇性低水平铅暴露会引发焦虑症，高血压，植物神经功能紊乱和神经炎症

背景

在发育阶段暴露于铅（Pb）会改变正常的发育过程，对健康产生终身影响。永久性铅暴露会导致行为改变，认知障碍，交感神经兴奋，心动过速，高血压和植物神经功能紊乱。但是，尚未研究间歇性铅暴露的影响。由于移民，学校交换计划的实施和/或居住环境的改变，这种接触方式最近一直在增加。

客观的

为了确定和比较铅对哺乳动物的行为和生理的影响，使用了间歇性和永久性Pb暴露的大鼠模型。

方法

在整个生命过程中，胎儿间歇性（PbI）或永久性（PbP）接触含乙酸铅（0.2％w / v）的水，直至成年（28周龄）。还使用了没有铅暴露的对照组（CTL）。

通过高架迷宫（EPM）和运动活动评估焦虑，并通过开放野外试验（OFT）评估焦虑。评估血压（BP），心电图（ECG），心率（HR），呼吸频率（RF），交感和副交感活动以及气压和化学感受器反射曲线。在海马区进行了免疫组织化学方案，以评估神经炎症，神经元丢失（NeuN），神经胶质增生和突触改变（Iba-1，GFAP，Syn）。统计分析采用单向方差分析和均值之间的多重比较（显着性p <0.05）。

结果

间歇性铅暴露使舒张压和平均BP值显着增加，同时伴有交感神经过度活动的趋势（通过低频能量的增加来估计），并且收缩压，HR和RF没有明显变化。还观察到化学感受器超敏反应和压力反射反射障碍，但是与永久性暴露相比，这种反应不太明显。关于行为变化，两种铅暴露曲线均表现出焦虑样行为，而运动和探索活动没有变化。在两个暴露组中都发现GFAP和Iba-1阳性细胞增加，而NeuN阳性细胞没有变化。Syn染色在PbI组中显着降低，而在PbP组中显着升高。

结论

这项研究首次表明自胎儿时期以来发育中的铅暴露会导致生理参数的持久损伤。间歇性铅暴露会对健康产生不利影响，例如，与永久性暴露相似，但在某些方面类似于高血压，呼吸频率增加和化学反射敏感性，压力反射受损，焦虑，突触活动减少，神经炎症和反应性神经胶质增生，但是其中一些是低度暴露，由于暴露时间较短。

这项研究对影响发育过程中自主神经系统和心血管系统的环境因素提供了新的见解，可以帮助制定预防和控制Pb毒性不利影响的公共政策策略。