Combined exposure of lead and cadmium leads to the aggravated neurotoxicity through regulating the expression of histone deacetylase 2

Autor: Hui-Li Wang, Jing Zhao, Ruiqing Zhou, Yanyan Xiao, Danyang Li, Anni Fan, Xiang-Tao Chen, Yao Chen
Rok vydání: 2019
Předmět:
Male
Environmental Engineering
Neurite
Health
Toxicology and Mutagenesis
Dendritic Spines
0208 environmental biotechnology
Central nervous system
Morris water navigation task
Histone Deacetylase 2
02 engineering and technology
010501 environmental sciences
Pharmacology
Hippocampal formation
Hydroxamic Acids
01 natural sciences
Hippocampus
Nervous System
PC12 Cells
Rats
Sprague-Dawley
Memory
medicine
Environmental Chemistry
Animals
Learning
0105 earth and related environmental sciences
Histone deacetylase 2
Chemistry
Public Health
Environmental and Occupational Health
Neurotoxicity
General Medicine
General Chemistry
medicine.disease
Pollution
020801 environmental engineering
Rats
medicine.anatomical_structure
Trichostatin A
Lead
Neurotoxicity Syndromes
Histone deacetylase
medicine.drug
Cadmium
Zdroj: Chemosphere. 252
ISSN: 1879-1298
Popis: 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.
Databáze: OpenAIRE
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