Department of Physiology, Faculty of Medicine Diponegoro University, Tembalang Semarang, 50275, Indonesia.
Department of Public Health, Faculty of Medicine Diponegoro University, Semarang, 50275, Indonesia.
Neurotox Res. 2020 Apr;37(4):827-834. doi: 10.1007/s12640-020-00174-4. Epub 2020 Feb 10.
Methylmercury (MeHg) is a well-known neurotoxin of the central nervous system (CNS). Neuroinflammation is one of the main pathways of MeHg-induced CNS impairment. This study aims to investigate the expressions of IL-6, MIP-2, and MCP-5, as biomarkers in relation with MeHg-induced CNS impairment and N-acetyl-L-cysteine (NAC) treatment in mice, as well as histopathological changes of brain tissue and clinical symptom such as ataxia. Twenty male Balb/c mice, aged 8-9 weeks, were divided into 4 groups and treated with saline (control), NAC [150 mg/kg body weight (BW) day], MeHg (4 mg Hg/kg BW), or a combination of MeHg and NAC for 17 days. MeHg induced the expression of IL-6, MIP-2, and MCP-5 in the serum, with median values (those in controls) of 55.06 (9.44), 15.94 (9.30), and 458.91 (239.91) mg/dl, respectively, and a statistical significance was observed only in IL-6 expression (p < 0.05). MIP-2 and MCP-5 expressions tended to increase in the cerebrum of MeHg-treated group compared with controls; however, the difference was not statistically significant. MeHg treatment also increased IL-6 expression in the cerebellum (7.73 and 4.81 mg/dl in MeHg-treated group and controls, respectively), with a marginal significance. NAC significantly suppressed MeHg-induced IL-6 and MIP-2 expressions in the serum (p < 0.05 for both), and slightly reduced MCP-5 expression in the cerebrum. Ataxia was observed in all MeHg-treated mice after 9-day exposure as well as the decrease of intact Purkinje cells in brain tissue (p < 0.05). These findings suggest that MeHg induced neurotoxicity by elevating the expression of IL-6, MIP-2, and MCP-5 and causing ataxia symptoms, and NAC reduced MeHg-mediated effects on the CNS.
甲基汞（MeHg）是一种众所周知的中枢神经系统（CNS）神经毒素。神经炎症是 MeHg 引起的 CNS 损伤的主要途径之一。本研究旨在探讨 IL-6、MIP-2 和 MCP-5 的表达，作为与 MeHg 引起的 CNS 损伤相关的生物标志物，以及 N-乙酰-L-半胱氨酸（NAC）在小鼠中的治疗作用，以及脑组织的组织病理学变化和共济失调等临床症状。将 20 只 8-9 周龄雄性 Balb/c 小鼠分为 4 组，分别用生理盐水（对照组）、NAC[150mg/kg 体重（BW）天]、MeHg（4mgHg/kgBW）或 MeHg 和 NAC 联合处理 17 天。MeHg 诱导血清中 IL-6、MIP-2 和 MCP-5 的表达，中位数（对照组）分别为 55.06（9.44）、15.94（9.30）和 458.91（239.91）mg/dl，仅在 IL-6 表达中观察到统计学意义（p<0.05）。与对照组相比，MeHg 处理组大脑中的 MIP-2 和 MCP-5 表达有增加的趋势，但差异无统计学意义。MeHg 处理还增加了小脑 IL-6 的表达（MeHg 处理组和对照组分别为 7.73 和 4.81mg/dl），差异具有边缘意义。NAC 显著抑制了血清中 MeHg 诱导的 IL-6 和 MIP-2 表达（两者均为 p<0.05），并略微降低了大脑中的 MCP-5 表达。所有 MeHg 处理的小鼠在 9 天暴露后都出现了共济失调，脑组织中完整的浦肯野细胞减少（p<0.05）。这些发现表明，MeHg 通过升高 IL-6、MIP-2 和 MCP-5 的表达并引起共济失调症状而导致神经毒性，NAC 减轻了 MeHg 对中枢神经系统的介导作用。
