論文 - 詳細
| RRC ID | 65624 |
|---|---|
| 著者 | Kimura E, Kohda M, Maekawa F, Fujii-Kuriyama Y, Tohyama C. |
| タイトル | Neurons expressing the aryl hydrocarbon receptor in the locus coeruleus and island of Calleja major are novel targets of dioxin in the mouse brain. |
| ジャーナル | Histochem Cell Biol |
| Abstract |
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. |
| 巻・号 | 156(2) |
| ページ | 147-163 |
| 公開日 | 2021-8-1 |
| DOI | 10.1007/s00418-021-01990-1 |
| PII | 10.1007/s00418-021-01990-1 |
| PMID | 33963922 |
| PMC | PMC8397641 |
| MeSH | Animals Basic Helix-Loop-Helix Transcription Factors / analysis Basic Helix-Loop-Helix Transcription Factors / genetics* Basic Helix-Loop-Helix Transcription Factors / metabolism Brain / metabolism* Dioxins / metabolism* Female Immunohistochemistry Locus Coeruleus / metabolism* Male Mice Mice, Inbred C57BL Mice, Knockout Neurons / metabolism* Receptors, Aryl Hydrocarbon / analysis Receptors, Aryl Hydrocarbon / genetics* Receptors, Aryl Hydrocarbon / metabolism |
| IF | 3.418 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | News |
| 各媒体での言及数の合計 | 1 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| 実験動物マウス | RBRC01710 |