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Environ Health Perspect. 2013 May;121(5):613-8. doi: 10.1289/ehp.1206066. Epub 2013 Feb 20.

AhR-mediated effects of dioxin on neuronal acetylcholinesterase expression in vitro.

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1
State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing, China.

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.

OBJECTIVES:

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.

PMID:
23426015
PMCID:
PMC3673198
DOI:
10.1289/ehp.1206066
[Indexed for MEDLINE]
Free PMC Article
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