Department of Toxicology, School of Public Health, China Medical University, #77 Puhe Road, Shenyang, 110122, People's Republic of China.
Department of Occupational and Environmental Health, School of Public Health, Jinzhou Medical University, #40 Section Three Songpo Road, Jinzhou, 121001, People's Republic of China.
Biol Trace Elem Res. 2019 Feb;187(2):482-491. doi: 10.1007/s12011-018-1402-2. Epub 2018 Jun 6.
Lanthanum could cause cognitive impairment in children and rodent animals. The normal blood-brain barrier (BBB) integrity is essential for protecting the brain from systemic toxins and maintaining the homeostasis for proper neuronal function. BBB dysfunction has been implicated as a potential mechanism of heavy metal-induced neurotoxicity. The present study was aimed to investigate effects of lanthanum on BBB integrity and endothelial junctional complexes in the cerebral cortex of young rats. Animals were exposed to lanthanum chloride (LaCl) through drinking water under 0, 0.25, 0.5, and 1.0% concentrations from postnatal day 0 until 30 days after weaning. LaCl-exposure increased BBB permeability, caused ultrastructure changes in cerebral capillaries, and reduced protein expression of claudin-5, occludin, and VE-cadherin. Due to the critical role of matrix metalloproteinases (MMPs) in BBB integrity, we further examined alterations in MMPs activity and expression. Enhanced gelatinase activity and upregulated MMP-9 expression were observed after LaCl-exposure, concurrently with decreased expression of endogenous inhibitor tissue inhibitors of metalloproteinase (TIMP)-1. Taken together, this study demonstrated that postnatal lanthanum exposure caused leakage of BBB in young rats, partially attributed to upregulation of MMP-9 and reduction of junctional proteins expression.
镧可能导致儿童和啮齿类动物认知障碍。正常的血脑屏障（BBB）完整性对于保护大脑免受全身毒素的侵害和维持适当神经元功能的内环境稳定至关重要。BBB 功能障碍已被认为是重金属诱导的神经毒性的潜在机制。本研究旨在研究镧对幼鼠大脑皮质 BBB 完整性和内皮连接复合体的影响。动物从出生后第 0 天开始通过饮用水暴露于氯化镧（LaCl），浓度分别为 0、0.25、0.5 和 1.0%，直到断奶后 30 天。LaCl 暴露增加了 BBB 通透性，导致脑毛细血管超微结构改变，并降低了紧密连接蛋白 5、occludin 和 VE-钙黏蛋白的蛋白表达。由于基质金属蛋白酶（MMPs）在 BBB 完整性中的关键作用，我们进一步研究了 MMPs 活性和表达的变化。LaCl 暴露后观察到明胶酶活性增强和 MMP-9 表达上调，同时内源性抑制剂金属蛋白酶组织抑制剂（TIMP）-1 的表达减少。总之，这项研究表明，出生后暴露于镧会导致幼鼠 BBB 渗漏，部分归因于 MMP-9 的上调和连接蛋白表达的减少。
