The Mammalian Circadian System Is Resistant to Dioxin

Apr 6, 2012Journal of biological rhythms

The body’s daily clock is resistant to dioxin

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Abstract

Treatment with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) did not affect the organization of the mouse circadian system.

AhR is a transcription factor activated by various environmental contaminants, including TCDD.
Previous studies suggest that AhR activation may impact circadian rhythms.
In vitro tests using tissues from PER2::LUCIFERASE mice showed no changes in circadian rhythm characteristics after TCDD treatment.
In vivo TCDD exposure did not alter the timing relationship between central and peripheral circadian oscillators.
These findings indicate that AhR activation by TCDD does not directly affect the circadian system in mice.

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The aryl hydrocarbon receptor (AhR) is a ligand-dependent transcription factor that is bound and activated by many toxic ubiquitous environmental contaminants, including the halogenated aromatic hydrocarbon, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). The AhR belongs to a family of proteins that contain basic helix-loop-helix/Per-ARNT-SIM (bHLH/PAS) domains. The circadian clock protein, BMAL1, is also a bHLH-PAS transcription factor and has been shown to interact with the AhR. AhRs are expressed in nearly every mammalian tissue, including the suprachiasmatic nuclei (SCN), and previous studies have suggested that activation of the AhR with dioxins affects rhythmicity in circadian clocks. In this study, the authors tested the hypothesis that activation of the aryl hydrocarbon receptor with the potent dioxin, TCDD, alters the organization of the mammalian circadian system by measuring bioluminescence from tissues explanted from PER2::LUCIFERASE mice. They found that in vitro treatment of explanted tissues with TCDD did not alter the periods, amplitudes, or damping rates of the PER2::LUC rhythms compared with controls. Likewise, in vivo treatment with TCDD had no effect on the phase relationship between central and peripheral oscillators. Together, these data demonstrate that activation of the AhR with TCDD does not directly or systemically alter the mouse circadian system.

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The Mammalian Circadian System Is Resistant to Dioxin

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