Neurons expressing the aryl hydrocarbon receptor in the locus coeruleus and island of Calleja major are novel targets of dioxin in the mouse brain

AbstractThe aryl hydrocarbon receptor (AhR) acts as a receptor that responds to ligands, including dioxin. The AhR –ligand complex translocates from the cytoplasm into the nucleus to induce gene expression. Because dioxin exposure impairs cognitive and neurobehavioral functions, AhR-expressing neurons need to be identified for elucidation of the dioxin neurotoxicity mechanism. Immunohistochemistry was performe d to detect AhR-expressing neurons in the mouse brain and confirm the specificity of the anti-AhR antibody usingAhr−/− mice. Intracellular distribution of AhR and expression level of AhR-target genes,Cyp1a1,Cyp1b1, andAhr repressor (Ahrr), were analyzed by immunohistochemistry and quantitative RT-PCR, respectively, using mice exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). The mouse brains were shown to harbor AhR in neurons of the locus coeruleus (LC) and island of Calleja major (ICjM) during developmental period inAhr+/+ mice but not inAhr−/− mice. A significant increase in nuclear AhR of ICjM neurons but not LC neurons was found in 14-day-old mice compared to 5- and 7-day-old mice. AhR was significantly translocated into the nucleus in LC and ICjM neurons of TCDD-exposed adult mice. Additionally, the expression levels ofCyp1a1,Cyp1b1, andAhrr genes in the brain, a surrogate of TCDD in the tissue, were significantly increased by dioxin exposure, suggesting that dioxin-activated AhR induces gene expression in LC and ICjM neurons. This histochemical stu...
Source: Histochemistry and Cell Biology - Category: Biomedical Science Source Type: research