Gas chromatography-mass spectrometry based metabolomics profile of hippocampus and cerebellum in mice after chronic arsenic exposure.
Gas chromatography-mass spectrometry based metabolomics profile of hippocampus and cerebellum in mice after chronic arsenic exposure.
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慢性砷暴露后小鼠海马和小脑基于气相色谱-质谱的代谢组学特征
DOI：
10.1002/tox.22662
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发表时间：
2018
影响因子：
4.5
通讯作者：
Xi
中科院分区：
文献类型：
--
作者：
Mo Ting-Ting;Dai Hua;Du Hang;Zhang Rui-Yuan;Chai Ke-Ping;An Yao;Chen Ji-Ji;Wang Jun-Ke;Chen Zi-Jin;Chen Cheng-Zhi;Jiang Xue-Jun;Tang Rong;Wang Li-Ping;Tan Qiang;Tang Ping;Miao Xin-Yu;Meng Pan;Zhang Long-Bin;Cheng Shu-Qun;Peng Bin;Tu Bai-Jie;Han Ting-Li;Xi
通过饮用水摄入砷（As）已对全球公共健康构成严重威胁。砷的神经毒性研究虽有大量报道，但其发病机制尚不明确，尤其是砷对代谢网络的慢性影响。海马是一个与学习和记忆有关的著名区域，而最近，小脑被认为与认知过程有关。因此，本研究旨在探讨慢性砷暴露后这两个区域的代谢组学变化，以进一步阐明砷神经毒性的细节。将12只3周龄雄性C57 BL/6 J小鼠分为两组，接受去离子饮用水（对照组）或50 mg/L亚砷酸钠（通过饮用水）24周。采用Morris水迷宫（MWM）测试大鼠的学习记忆能力。透射电镜观察海马和小脑的病理形态学变化。通过气相色谱-质谱法（GC-MS）分析代谢变化。MWM实验证实慢性砷暴露可引起小鼠学习记忆能力的损害。代谢组学鉴定结果表明，海马和小脑中酪氨酸含量增加，天冬氨酸含量减少。小脑中琥珀酸和三羧酸循环的间接参与成分脯氨酸、半胱氨酸和丙氨酸的含量下降，表明能量代谢紊乱。我们的研究结果表明，这些代谢物的变化与砷引起的氨基酸和能量代谢紊乱有关，因此，这可能在砷神经毒性机制中起重要作用。
Intake of arsenic (As) via drinking water has been a serious threat to global public health. Though there are numerous reports of As neurotoxicity, its pathogenesis mechanisms remain vague especially its chronic effects on metabolic network. Hippocampus is a renowned area in relation to learning and memory, whilst recently, cerebellum is argued to be involved with process of cognition. Therefore, the study aimed to explore metabolomics alternations in these two areas after chronic As exposure, with the purpose of further illustrating details of As neurotoxicity. Twelve 3‐week‐old male C57BL/6J mice were divided into two groups, receiving deionized drinking water (control group) or 50 mg/L of sodium arsenite (via drinking water) for 24 weeks. Learning and memory abilities were tested by Morris water maze (MWM) test. Pathological and morphological changes of hippocampus and cerebellum were captured via transmission electron microscopy (TEM). Metabolic alterations were analyzed by gas chromatography‐mass spectrometry (GC‐MS). MWM test confirmed impairments of learning and memory abilities of mice after chronic As exposure. Metabolomics identifications indicated that tyrosine increased and aspartic acid (Asp) decreased simultaneously in both hippocampus and cerebellum. Intermediates (succinic acid) and indirect involved components of tricarboxylic acid cycle (proline, cysteine, and alanine) were found declined in cerebellum, indicating disordered energy metabolism. Our findings suggest that these metabolite alterations are related to As‐induced disorders of amino acids and energy metabolism, which might therefore, play an important part in mechanisms of As neurotoxicity.