Waterborne manganese exposure alters plasma, brain, and liver metabolites accompanied by changes in stereotypic behaviors.
Waterborne manganese exposure alters plasma, brain, and liver metabolites accompanied by changes in stereotypic behaviors.
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DOI：
10.1016/j.ntt.2011.10.003
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发表时间：
2012-01
影响因子：
2.9
通讯作者：
Erikson, Keith M.
中科院分区：
文献类型：
--
作者：
Fordahl, Steve;Cooney, Paula;Qiu, Yunping;Xie, Guoxiang;Jia, Wei;Erikson, Keith M.
在其他实验模型中，水溶性锰（Mn）过量与儿童的认知障碍和神经化学异常有关。为了表征锰暴露和改变的神经化学之间的阈值，重要的是要确定与脑锰积累正对应的生物标志物。本研究的目的是确定锰诱导的血浆，肝脏和脑代谢物的改变，使用液相/气相色谱-飞行时间-质谱代谢组学分析，并监测相应的锰诱导的行为变化。断奶Sprague-Dawley大鼠可以获得无Mn或含有1g Mn/L的去离子饮用水6周。在第六周期间，使用视频监控在家庭笼环境中连续24小时监测行为。锰暴露显着增加肝脏，血浆和脑锰浓度相比，控制，专门针对苍白球（GP）。锰显著改变了大脑、肝脏和血浆中的98种代谢物;特别是改变了大脑（增加油酸和棕榈酸;分别为12.57和15.48倍变化（FC））和肝脏（增加油酸，14.51 FC;减少羟基丁酸，-14.29 FC）中的胆固醇和脂肪酸代谢。此外，锰改变血浆代谢物尿黑酸，鹅去氧胆酸，天冬氨酸与GP和纹状体锰显着相关。总距离旅行显着增加，正相关与锰暴露，而夜间刻板和探索行为减少锰暴露，主要是在光周期相比，未暴露的大鼠。这些数据提供了锰神经毒性的推定生物标志物，并表明锰破坏了大鼠的昼夜节律周期。
Overexposure to waterborne manganese (Mn) is linked with cognitive impairment in children and neurochemical abnormalities in other experimental models. In order to characterize the threshold between Mn-exposure and altered neurochemistry, it is important to identify biomarkers that positively correspond with brain Mn-accumulation. The objective of this study was to identify Mn-induced alterations in plasma, liver, and brain metabolites using liquid/gas chromatography-time of flight-mass spectrometry metabolomic analyses; and to monitor corresponding Mn-induced behavior changes. Weanling Sprague-Dawley rats had access to deionized drinking water either Mn-free or containing 1g Mn/L for six weeks. Behaviors were monitored during the sixth week for a continuous 24h period while in a home cage environment using video surveillance. Mn-exposure significantly increased liver, plasma, and brain Mn concentrations compared to control, specifically targeting the globus pallidus (GP). Mn significantly altered 98 metabolites in the brain, liver, and plasma; notably shifting cholesterol and fatty acid metabolism in the brain (increased oleic and palmitic acid; 12.57 and 15.48 fold change (FC), respectively), and liver (increased oleic acid, 14.51 FC; decreased hydroxybutyric acid, −14.29 FC). Additionally, Mn-altered plasma metabolites homogentisic acid, chenodeoxycholic acid, and aspartic acid correlated significantly with GP and striatal Mn. Total distance traveled was significantly increased and positively correlated with Mn-exposure, while nocturnal stereotypic and exploratory behaviors were reduced with Mn-exposure and performed largely during the light cycle compared to unexposed rats. These data provide putative biomarkers for Mn-neurotoxicity and suggest that Mn disrupts the circadian cycle in rats.
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影响因子：
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通讯作者：
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