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1373 Time sequence of oxidative stress in neurodegenerative brain after long-term lead exposure in rats
  1. Chang Feng1,
  2. Yanyan Gao1,
  3. Yanshu Li1,2,
  4. Fankun Zhou1,
  5. Shuyun Zhang1,
  6. Gaochun Zhu3,
  7. Guihua Du1,
  8. Ying Chen1,
  9. Huan Jiao1,
  10. Ji Yan1,
  11. Jiangao Feng1,
  12. Guangqin Fan1
  1. 1Department of Occupational Health and Toxicology, School of Public Health, Nanchang University, Nanchang 330006, China
  2. 2Institute of Materia Medica of Jiangxi province, Nanchang 330029, China
  3. 3Department of Anatomy, School of Medicine, Nanchang University, Nanchang 330006, China


Introduction A large number of studies have shown that the developmental neurotoxicity induced by lead is related to oxidative injury, meanwhile, oxidative stress is among the most common mechanisms of neurodegeneration. However, few studies have explored the role of oxidative stress in age-related cognitive impairment caused by prolonged lead exposure and oxidative stress.

Methods In the present study, rats were exposed to low-level lead from the embryonic stage to old age. Dynamic changes in neurodegeneration, endoplasmic reticulum (ER) stress, and oxidative stress in brains during postnatal weeks 3, 41 and 70 (PNW3, PNW41 and PNW70, respectively) were investigated.

Results Lead exposure resulted in neurodegeneration in PNW70 rats based on magnetic resonance imaging (MRI) scans and thionine stain analysis. Amyloid precursor protein (APP) and tau mRNA expression in PNW41 and PNW70 brains increased in a time- and dose-dependent manner. APP and Tau protein levels significantly increased with lead exposure at PNW3 and PNW70. Mechanistically, the expression of the ER stress protein glucose-regulated protein 78 (GRP78) was higher in the presence of lead than in normal controls, which was associated with high levels of 8-hydroxy-2’-deoxyguanosine (8-OHdG) in brain tissues after lead exposure in PNW3 and PNW70, their changes were like as APP and tau protein that were a u- or j-shaped curve with time of lead exposure.

Conclusion Our findings suggest that the neurodegenerative injuries induced by lead exposure may be mediated by ER and oxidative stresses, and there is a critical period for prevention or intervention AD in early life and later life, however middle-aged people at the latent stage of neurodegenerative process should not be ignored.

  • lead
  • neurodegenerative diseases
  • oxidative stress

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