Department of Environmental Health, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences.
Department of Environmental Health, Faculty of Pharmaceutical Sciences, Tokyo University of Science.
J Toxicol Sci. 2019;44(8):549-558. doi: 10.2131/jts.44.549.
Methylmercury (MeHg) exposure is known to induce neurodegeneration in both the central nervous system (CNS) and peripheral nervous system (PNS). Molecular mechanisms of MeHg-induced neurotoxicity have been well investigated in the CNS, however, it remains unclear in the PNS. In the present study, comprehensive gene expression analysis was performed by analyzing MeHg-exposed adult rat dorsal root ganglion (DRG) by DNA microarray. Methylmercuric chloride (6.7 mg/kg/day) was administered to nine-week-old male Wistar rats for five days, followed by two days without administration; this cycle was repeated once. Rats were anesthetized at 7 or 14 days after commencement of MeHg exposure, and their DRGs were removed and homogenized to make total RNA samples. DNA microarray data from Day 7 samples identified 100 out of 18,513 detected genes as annotated genes with more than two-fold upregulated or downregulated expression compared with controls. Database for Annotation, Visualization, and Integrated Discovery (DAVID) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses suggested strong involvement of immune activation and inflammation pathways in rat DRG exposed to MeHg, and some genes overlapped with previously reported genes affected by MeHg exposure in the cerebellum. The present results suggest that MeHg-induced neurotoxicity is associated with immune activation and inflammatory responses in rat DRG.
甲基汞（MeHg）暴露已知会导致中枢神经系统（CNS）和周围神经系统（PNS）的神经退行性变。MeHg 诱导的神经毒性的分子机制在 CNS 中得到了很好的研究，但在 PNS 中仍不清楚。在本研究中，通过 DNA 微阵列分析暴露于 MeHg 的成年大鼠背根神经节（DRG）进行了全面的基因表达分析。将氯化甲基汞（6.7mg/kg/天）施用于 9 周龄雄性 Wistar 大鼠，连续 5 天，然后停止给药 2 天；此周期重复一次。在开始暴露于 MeHg 后第 7 天或第 14 天麻醉大鼠，并取出其 DRG 并匀浆以制备总 RNA 样品。与对照组相比，第 7 天样本的 DNA 微阵列数据鉴定出 18513 个检测到的基因中的 100 个为注释基因，其表达水平上调或下调超过两倍。数据库注释、可视化和综合发现（DAVID）和京都基因与基因组百科全书（KEGG）途径分析表明，MeHg 暴露的大鼠 DRG 中强烈涉及免疫激活和炎症途径，一些基因与先前报道的 MeHg 暴露在小脑中影响的基因重叠。本研究结果表明，MeHg 诱导的神经毒性与大鼠 DRG 中的免疫激活和炎症反应有关。
