title: AhR-mediated effects of dioxin on neuronal acetylcholinesterase expression in vitro.
abstract: BACKGROUND
  Deficits in cognitive functioning have been reported in humans exposed to dioxins and dioxin-like compounds. Evidence suggests that dioxins induce cholinergic dysfunction mediated by hypothyroidism. However, little is known about direct effects of dioxins on the cholinergic system.
  
  
  OBJECTIVE
  We investigated the action of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on acetylcholinesterase (AChE), a key enzyme in cholinergic neurotransmission.
  
  
  METHODS
  We used SK-N-SH human-derived neuronal cells to evaluate the effect of dioxin exposure on AChE.
  
  
  RESULTS
  We consistently found a significant decrease in enzymatic activity of AChE in cultured neurons treated with TCDD. We also found that, unlike organophosphate pesticides that directly act on the catalytic center of AChE, the suppressive effect of dioxin was through transcriptional regulation. The addition of CH223191, an inhibitor of the aryl hydrocarbon receptor (AhR)-dependent pathway, counteracted the TCDD-induced suppression of AChE, suggesting involvement of the AhR-dependent pathway. The existence of putative dioxin-responsive element (DRE) consensus sequences in the human ACHE promoter region further supported this hypothesis. Consistent with the absence of DRE elements in mouse or rat ACHE promoter regions, suppression of AChE by TCDD did not occur in rat neuronal cells, indicating a potential species-specific effect.
  
  
  CONCLUSIONS
  In SK-N-SH cells, dioxin suppressed the activity of neuronal AChE via AhR-mediated transcriptional down-regulation. This is the first study to report direct interference by dioxin with the cholinergic neurotransmission system.
authors: State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing, China.
authors: Heidi Qunhui
authors: HQ
authors: Xie
authors: Hai-Ming
authors: HM
authors: Xu
authors: Hua-Ling
authors: HL
authors: Fu
authors: Qin
authors: Q
authors: Hu
authors: Wen-Jing
authors: WJ
authors: Tian
authors: Xin-Hui
authors: XH
authors: Pei
authors: Bin
authors: B
authors: Zhao
mesh_terms: D000110:Acetylcholinesterase / Q000235:genetics*; D000818:Animals; D001391:Azo Compounds / Q000494:pharmacology; D045744:Cell Line, Tumor; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects*; D006801:Humans; D051379:Mice; D009474:Neurons / Q000187:drug effects* / Q000201:enzymology; D016716:PC12 Cells; D000072317:Polychlorinated Dibenzodioxins / Q000633:toxicity*; D011720:Pyrazoles / Q000494:pharmacology; D051381:Rats; D018336:Receptors, Aryl Hydrocarbon / Q000502:physiology*
chemical_list: C511621:2-methyl-2H-pyrazole-3-carboxylic acid (2-methyl-4-o-tolylazophenyl)amide; D001391:Azo Compounds; D000072317:Polychlorinated Dibenzodioxins; D011720:Pyrazoles; D018336:Receptors, Aryl Hydrocarbon; D000110:Acetylcholinesterase