Abstract
The aryl hydrocarbon receptor (or AhR) is a cytoplasmic receptor of pollutants. It translocates into the nucleus upon binding to its ligands, and forms a heterodimer with ARNT (AhR nuclear translocator). The heterodimer is a transcription factor, which regulates the transcription of xenobiotic metabolizing enzymes. Expressed in many cells in vertebrates, it is mostly present in neuronal cell types in invertebrates, where it regulates dendritic morphology or feeding behavior. Surprisingly, few investigations have been conducted to unravel the function of the AhR in the central or peripheral nervous systems of vertebrates. In this review, we will present how the AhR regulates neural functions in both invertebrates and vertebrates as deduced mainly from the effects of xenobiotics. We will introduce some of the molecular mechanisms triggered by the well-known AhR ligand, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), which impact on neuronal proliferation, differentiation, and survival. Finally, we will point out the common features found in mice that are exposed to pollutants, and in AhR knockout mice.
Highlights
The aryl hydrocarbon receptor (AhR) is a protein that belongs to the PAS (Per-ARNT-Sim) family and contains a basic helix-loop-helix domain
This is coherent with genome-wide association studies (GWAS) that show an association between AhR expression and the severity of major depressive disorders [181], or by a recent study on the damages induced by the KYN/AhR following experimental stroke [182]
The AhR is expressed in several neural cell types including neurons, astrocytes or microglial cells
Summary
The aryl hydrocarbon receptor (AhR) is a protein that belongs to the PAS (Per-ARNT-Sim) family and contains a basic helix-loop-helix domain. Binding to a ligand presumably induces a conformational change in the AhR and leads to dissociation of the complex, which translocates into the nucleus where it interacts with ARNT (aryl hydrocarbon nuclear translocator or hypoxia-inducible factor-1ß), to forms a transcription factor. This heterodimer binds to xenobiotic-responsive elements (XRE) in the promoters of target genes, and regulates their transcription in part, to control xenobiotic metabolism. In the invertebrate nematode model, Caenorhabditis elegans, AHR-1 displays some interesting features [5,6,7,8] It does not bind 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), the prototypical ligand for the AhR of vertebrates. We will point out the common features found in mice exposed to pollutants and in AhR knockout mice
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