Kumasaka Mayuko Y, Yajima Ichiro, Ohgami Nobutaka, Naito Hisao, Omata Yasuhiro, Kato Masashi
Department of Occupational and Environmental Health, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, Aichi, 466-8550, Japan.
Arch Toxicol. 2014 May;88(5):1185-6. doi: 10.1007/s00204-014-1221-y. Epub 2014 Mar 11.
Krishna et al. (Arch Toxicol 88(1):47-64, 2014) recently published the results of a study in which adult C57BL/6 mice were subchronically exposed to 400,000 μg/L manganese (Mn) using manganese chloride via drinking water for 8 weeks and examined the neurotoxic effects. After 5 weeks of Mn exposure, significant deposition of Mn in all of the brain regions examined by magnetic resonance imaging was detected. After 6 weeks of Mn exposure, neurobehavioral deficits in an open field test, a grip strength test, and a forced swim test were observed. Eight weeks of Mn exposure increased striatal 5-hydroxyindoleacetic acid (a serotonin metabolite) levels, but did not alter the levels of striatal dopamine, its metabolites and serotonin. Krishna et al. also reported significant increases in mRNA levels of GFAP (an astrocyte activation marker), HO-1 (an oxidative stress marker) and NOS2 (a nitrosative stress marker), and in protein expression level of GFAP in the substantia nigra pars reticulata after 8 weeks of Mn exposure. These results suggest that 400,000 μg/L Mn exposure via drinking water in mice induces neurobehavioral deficits, serotonergic imbalance, and glial activation accompanied by an increase in brain Mn deposition. The report by Krishna et al. is interesting because the studies on the neurobehavioral effect of Mn exposure by drinking water in mice are very limited. However, Mn concentrations previously reported in well drinking water (Agusa et al. in Vietnam Environ Pollut 139(1):95-106, 2006; Buschmann et al. in Environ Int 34(6):756-764, 2008; Hafeman et al. in Environ Health Perspect 115(7):1107-1112, 2007; Wasserman et al. in Bangladesh Environ Health Perspect 114(1):124-129, 2006) were lower than 400,000 μg/L.
克里希纳等人（《毒理学文献》88(1):47 - 64, 2014年）最近发表了一项研究结果，该研究中成年C57BL/6小鼠通过饮用水以氯化锰形式亚慢性暴露于400,000μg/L的锰（Mn）中8周，并检测了神经毒性作用。锰暴露5周后，通过磁共振成像检测到在所有检测的脑区中锰有显著沉积。锰暴露6周后，在旷场试验、握力试验和强迫游泳试验中观察到神经行为缺陷。锰暴露8周后，纹状体5 - 羟色胺酸（一种血清素代谢物）水平升高，但纹状体多巴胺、其代谢物和血清素水平未改变。克里希纳等人还报告称，锰暴露8周后，黑质网状部中胶质纤维酸性蛋白（一种星形胶质细胞激活标志物）、血红素加氧酶 - 1（一种氧化应激标志物）和一氧化氮合酶2（一种亚硝化应激标志物）的mRNA水平以及胶质纤维酸性蛋白的蛋白表达水平均显著增加。这些结果表明，小鼠通过饮用水暴露于400,000μg/L的锰会诱发神经行为缺陷、血清素能失衡以及胶质细胞激活，并伴有脑内锰沉积增加。克里希纳等人的报告很有意思，因为关于小鼠通过饮用水暴露于锰的神经行为影响的研究非常有限。然而，先前在井水饮用水中报道的锰浓度（阿古萨等人，《越南环境污染》139(1):95 - 106, 2006年；布施曼等人，《环境国际》34(6):756 - 764, 2008年；哈夫曼等人，《环境健康展望》115(7):1107 - 1112, 2007年；瓦瑟曼等人，《孟加拉国环境健康展望》114(1):124 - 129, 2006年）低于400,000μg/L。
