Combined exposure of lead and cadmium leads to the aggravated neurotoxicity through regulating the expression of histone deacetylase 2. (August 2020)

• Record Type: Journal Article
• Authors: Zhou, Ruiqing; Zhao, Jing; Li, Danyang; Chen, Yao; Xiao, Yanyan; Fan, Anni; Chen, Xiang-Tao; Wang, Hui-Li
• Is Part Of: Chemosphere. Volume 252(2020)
• Publication Date: 2020-08
• Subjects: Pb -- Cd -- Co-exposure -- HDAC2 -- Dendritic spine; Pollution -- Periodicals; Pollution -- Physiological effect -- Periodicals; Environmental sciences -- Periodicals; Atmospheric chemistry -- Periodicals; 551.511
• DOI: 10.1016/j.chemosphere.2020.126589
• Languages: English
• ISSNs: 0045-6535

Abstract

Abstract: Lead (Pb) and cadmium (Cd) are common heavy metals in the environment, exerting detrimental effects on central nervous system. Although increasing evidence demonstrated the Pb and Cd-induced neurotoxicity, the exact epigenetic mechanisms induced by combined exposure (co-exposure) of Pb and Cd are still unclear. In this study, the neurotoxicity of individual exposure and co-exposure to Pb and Cd in vivo (150 ppm and 5 ppm respectively) and in vitro (10 μM and 0.1 μM respectively) was investigated . The results showed that neurite outgrowth was inhibited by either individual or combined exposure to Pb/Cd, whereas the co-exposure aggravated the inhibitory effect in PC12 cells. The results of Morris Water Maze (MWM), Y maze and Golgi-Cox staining showed that either Pb or Cd alone exposure damaged the ability of learning and memory and decreased the dendritic spine density in both the hippocampal CA1 and DG area of Sprague–­­Dawley (SD) rats, and that the co-exposure aggravated the damages. Subsequently, histone deacetylase (HDAC) 2 was significantly increased in both hippocampal tissues and PC12 cells co-exposed to Pb and Cd, and the treatment of trichostatin A (TSA) and HDAC2–knocking down construct (shHDAC2) could markedly prevent neurite outgrowth impairment in PC12 cells. In summary, HDAC2 plays essential regulatory roles in neurotoxicity induced by the co-exposure to Pb and Cd, providing a potential molecular target for neurological intervention. Highlights: The co-exposure to Pb and Cd aggravated the damage of learning and memory of SD rats. The co-exposure aggravated the reduction of dendritic spine density. HDAC2's expression was promoted by co-exposure in vivo and in vitro . TSA and shHDAC2 rescued the neurite outgrowth deficits caused by Pb and Cd.