Cardiovascular Centre of the University of Lisbon, Portugal.
Cardiovascular Centre of the University of Lisbon, Portugal; Institute of Physiology, Faculty of Medicine of the University of Lisbon, Portugal.
Neurotoxicology. 2018 Dec;69:307-319. doi: 10.1016/j.neuro.2018.08.001. Epub 2018 Aug 8.
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.
To determine and compare lead effects on mammal's behavior and physiology, using a rat model of intermittent and permanent Pb exposures.
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.
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.
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.
在发育阶段暴露于铅（Pb）会改变正常的发育过程，对终身健康造成影响。永久性 Pb 暴露会导致行为改变、认知障碍、交感兴奋、心动过速、高血压和自主神经功能障碍。然而，间歇性 Pb 暴露的影响尚未得到研究。由于移民、实施学校交流计划和/或居住环境改变，这种暴露模式最近一直在增加。
使用大鼠间歇性和永久性 Pb 暴露模型，确定和比较 Pb 对哺乳动物行为和生理的影响。
胎儿在整个生命过程中（直至成年，即 28 周龄）通过饮用水间歇性（PbI）或永久性（PbP）暴露于含有醋酸铅（0.2%w/v）的水中。还使用了一个没有任何 Pb 暴露的对照组（CTL）。焦虑通过高架十字迷宫（EPM）和旷场测试（OFT）评估的运动和探索行为进行评估。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压力和化学感受器反射谱进行评估。在海马体进行神经炎症、神经元丢失（NeuN）、神经胶质增生和突触改变（Iba-1、GFAP、Syn）的免疫组织化学评估。采用单因素方差分析（ANOVA）和 Tukey 多重比较进行均值比较（统计学意义 p<0.05）。
间歇性 Pb 暴露会导致舒张压和平均 BP 值显著升高，同时交感神经活动过度活跃（通过低频功率增加来估计），而收缩压、HR 和 RF 没有显著变化。还观察到化学感受器敏感性和压力感受器反射受损，但与永久性暴露相比，程度较轻。关于行为变化，两种 Pb 暴露模式均表现出类似焦虑的行为，而运动和探索活动没有变化。在两个暴露组中，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 组中显著减少，在 PbP 组中显著增加。
本研究首次表明，从胎儿期开始的发育性 Pb 暴露会导致生理参数的持续损害。间歇性 Pb 暴露会导致不良的健康影响，例如高血压、呼吸频率增加和化学感受器敏感性增加、压力感受器反射受损、焦虑、突触活动减少、神经炎症和反应性神经胶质增生，在某些方面类似于永久性暴露，但由于暴露时间较短，某些影响程度较轻。本研究为影响发育过程中自主和心血管系统的环境因素提供了新的见解，这有助于制定公共政策策略，以预防和控制 Pb 毒性的不良影响。
