Abstract
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.