Guimarães D, Santos J P, Carvalho M L, Diniz M S, House B, Miller V M
Centro de Física Atómica da Universidade de Lisboa, Departamento de Física, Faculdade de Ciências e Tecnologia, FCT, Universidade Nova de Lisboa, 2829-516 Caparica, Portugal; Laboratory of Inorganic and Nuclear Chemistry, Wadsworth Center, New York State Department of Health, PO Box 509, Albany, NY 12201-0509, USA.
Centro de Física Atómica da Universidade de Lisboa, Departamento de Física, Faculdade de Ciências e Tecnologia, FCT, Universidade Nova de Lisboa, 2829-516 Caparica, Portugal.
Neurotoxicology. 2014 Sep;44:91-7. doi: 10.1016/j.neuro.2014.05.010. Epub 2014 Jun 4.
Lead is a potent toxicant associated with adverse cardiovascular effects and hypertension in children. Yet, few studies have determined if autonomic dysfunction associated with lead exposure involves brain regions which regulate autonomic responses. Central autonomic nuclei such as the nucleus tractus solitarius (NTS) and hypothalamic defence area (HDA) may be particularly sensitive to lead infiltration because they are adjacent to ventricles and areas with semi-permeable blood-brain-barriers. To understand if autonomic nuclei are sensitive to lead accumulation Wistar rats were exposed to lead from the gestational period and lead levels were quantified in brain regions that regulate arterial pressure: the NTS and the HDA. Energy dispersive X-ray fluorescence (EDXRF) was used to quantify total brain lead levels and revealed no differences between exposed and control tissues; measured values were close to the detection limit (2μg/g). Electrothermal atomic absorption spectrometry (ETAAS) was also used, which has a greater sensitivity, to quantify lead. There was ∼2.1μg/g lead in the NTS and ∼3.1μg/g lead in the HDA of exposed rats, and no lead in the control rats. There were greater lead levels in the HDA (∼50%) as compared with the NTS. Pathology studies revealed more prominent lead granules in the HDA as compared with the NTS. Increased microglia and astrocyte activation was also noted in the NTS of lead exposed rats as compared with the HDA. Regional differences in neuro-inflammatory responses likely contribute to heterogeneous lead accumulation, with enhanced clearance of lead in the NTS. Future studies will resolve the mechanisms underpinning tissue-specific lead accumulation.
铅是一种强效毒物，与儿童心血管不良影响和高血压有关。然而，很少有研究确定与铅暴露相关的自主神经功能障碍是否涉及调节自主反应的脑区。中枢自主神经核，如孤束核（NTS）和下丘脑防御区（HDA），可能对铅浸润特别敏感，因为它们与脑室和具有半透性血脑屏障的区域相邻。为了解自主神经核是否对铅积累敏感，将Wistar大鼠从妊娠期开始暴露于铅，并对调节动脉血压的脑区（NTS和HDA）中的铅水平进行定量。能量色散X射线荧光光谱法（EDXRF）用于定量全脑铅水平，结果显示暴露组和对照组组织之间没有差异；测量值接近检测限（2μg/g）。还使用了灵敏度更高的电热原子吸收光谱法（ETAAS）来定量铅。暴露组大鼠的NTS中铅含量约为2.1μg/g，HDA中约为3.1μg/g，对照组大鼠中无铅。与NTS相比，HDA中的铅含量更高（约50%）。病理学研究显示，与NTS相比，HDA中的铅颗粒更明显。与HDA相比，铅暴露大鼠的NTS中还观察到小胶质细胞和星形胶质细胞激活增加。神经炎症反应的区域差异可能导致铅积累的异质性，NTS中铅的清除增强。未来的研究将阐明组织特异性铅积累的潜在机制。
