Oxidative stress in the neurodegenerative brain following lifetime exposure to lead in rats: Changes in lifespan profiles
Oxidative stress in the neurodegenerative brain following lifetime exposure to lead in rats: Changes in lifespan profiles
复制标题
大鼠终生接触铅后神经退行性大脑的氧化应激：寿命曲线的变化
DOI：
10.1016/j.tox.2018.11.003
复制
发表时间：
2019-01-01
期刊：
影响因子：
4.5
通讯作者：
Fan, Guangqin
中科院分区：
文献类型：
--
作者：
Feng, Chang;Liu, Sisi;Fan, Guangqin
大量研究表明，铅的发育神经毒性与氧化损伤有关。此外，最近的研究发现，发育性铅暴露可导致老年神经退行性变。由于铅在环境中的普遍存在，人类在一生中都会接触到这种金属。然而，很少有研究探讨终生铅暴露后神经毒性和氧化应激寿命曲线的变化。在本研究中，大鼠从胚胎阶段到老年都暴露于醋酸铅。观察出生后3周(PNW3，断奶)、41周(PNW41，成年期)和70周(PNW70，老年)大鼠脑内神经退行性变、氧化应激和内质网应激的动态变化。铅暴露导致PNW3和PNW70大鼠神经元变性，神经元密度和脑体积减少；然而，基于硫氨酸染色分析和磁共振成像(MRI)扫描，PNW41大鼠没有明显变化。PNW3和PNW70大鼠铅暴露后脑内8-羟基-2‘-脱氧鸟苷(8-OHdG)水平升高与内质网应激蛋白葡萄糖调节蛋白78(GRP78)表达增加有关。我们的研究结果表明，终生铅暴露引起的神经退行性损伤始于婴儿期，成年后缓解，但在老年时加剧。预防或干预铅暴露所致神经退行性疾病的关键时期出现在生命早期。
A large number of studies have evidenced that developmental neurotoxicity induced by lead (Pb) is related to oxidative injury. Furthermore, recent studies have found that developmental Pb exposure can induce neurodegeneration in old age. Because of the common presence of Pb in the environment, humans are exposed to this metal throughout their lifetime. However, few studies have explored the changes in lifespan profiles of neurotoxicity, as well as oxidative stress following lifetime Pb exposure. In the present study, rats were exposed to lead acetate from their embryonic stage to old age. Dynamic changes in neurodegeneration, oxidative stress, and endoplasmic reticulum (ER) stress in the brains at postnatal week 3 (PNW3, weaning), 41 weeks (PNW41, adulthood) and 70 weeks (PNW70, old age) were investigated. Pb exposure resulted in neurodegeneration with decreased neuronal densities and brain volumes in PNW3 and PNW70 rats; however, no significant changes occurred in PNW41 rats based on thionine stain analysis and magnetic resonance imaging (MRI) scans. Expression of the ER stress protein glucose-regulated protein 78 (GRP78) increased in Pb-exposed rats, which was associated with high levels of 8-hydroxy-2'-deoxyguanosine (8-OHdG) in rat brains after Pb exposure in PNW3 and PNW70 rats. Our findings suggested that lifetime Pb exposure induced neurodegenerative injuries that began to occur in infancy, were relieved in adulthood, but intensified in old age. The critical periods for prevention or intervention in neurodegenerative diseases induced by Pb exposure occurred in early life.