The 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 performed to detect AhR-expressing neurons in the mouse brain and confirm the specificity of the anti-AhR antibody using Ahr^−/− mice. Intracellular distribution of AhR and expression level of AhR-target genes, Cyp1a1, Cyp1b1, and Ahr 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 in Ahr^+/+ mice but not in Ahr^−/− 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 of Cyp1a1, Cyp1b1, and Ahrr 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 study shows the ligand-induced nuclear translocation of AhR at the single-neuron level in vivo. Thus, the neurotoxicological significance of the dioxin-activated AhR in the LC and ICjM warrants further studies.

芳烃受体 (AhR) 是一种对配体（包括二恶英）有反应的受体。AhR-配体复合物从细胞质转移到细胞核中以诱导基因表达。由于二恶英暴露会损害认知和神经行为功能，因此需要鉴定表达 AhR 的神经元以阐明二恶英的神经毒性机制。进行免疫组织化学以检测小鼠大脑中表达AhR的神经元并使用Ahr ^-/-小鼠确认抗AhR抗体的特异性。AhR 的细胞内分布和 AhR 靶基因Cyp1a1、Cyp1b1和Ahr 阻遏物( Ahrr ) 的表达水平)，分别通过免疫组织化学和定量 RT-PCR 分析，使用暴露于 2,3,7,8-四氯二苯并-对-二恶英 (TCDD) 的小鼠。在Ahr ^+/+小鼠的发育期间，小鼠大脑在蓝斑 (LC) 和 Calleja major 岛 (ICjM) 的神经元中显示出携带 AhR，但在Ahr ^-/-小鼠中则没有。与 5 天和 7 天大的小鼠相比，在 14 天大的小鼠中发现 ICjM 神经元的核 AhR 显着增加，而不是 LC 神经元。在暴露于 TCDD 的成年小鼠的 LC 和 ICjM 神经元中，AhR 显着易位到细胞核中。此外，Cyp1a1、Cyp1b1和Ahrr的表达水平大脑中的基因（组织中 TCDD 的替代物）因暴露于二恶英而显着增加，这表明二恶英激活的 AhR 诱导了 LC 和 ICjM 神经元中的基因表达。该组织化学研究显示了配体诱导的 AhR 在体内单神经元水平的核转位。因此，二恶英激活的 AhR 在 LC 和 ICjM 中的神经毒理学意义值得进一步研究。