Postnatal Subacute Benzo(a)Pyrene Exposure Caused Neurobehavioral Impairment and Metabolomic Changes of Cerebellum in the Early Adulthood Period of Sprague-Dawley Rats
Postnatal Subacute Benzo(a)Pyrene Exposure Caused Neurobehavioral Impairment and Metabolomic Changes of Cerebellum in the Early Adulthood Period of Sprague-Dawley Rats
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出生后亚急性苯并(a)芘暴露引起成年早期斯普拉格-道利大鼠神经行为损伤和小脑代谢组变化
DOI：
10.1007/s12640-017-9832-8
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发表时间：
2018-05
影响因子：
3.7
通讯作者：
涂白杰
中科院分区：
文献类型：
--
作者：
涂白杰
苯并(a)芘（BaP）是一种广泛存在的环境污染物，与哺乳动物的神经毒性有关。它对发育中的中枢神经系统有很强的毒性作用。小脑与运动活动和焦虑行为有关，但关于BaP对小脑的毒性作用的研究很少。本研究旨在探讨BaP亚急性暴露对大鼠小脑代谢组的影响。雄性新生大鼠（出生后第5天）分为两组：对照组和bap处理组（2 mg/kg/d，连续7周）。采用开场实验和透射电镜观察大鼠神经行为和超微结构变化。采用气相色谱-质谱（GC-MS）分析两组小鼠小脑代谢物。结果显示，出生后暴露于BaP可促进成年早期小脑的病理改变，并增加运动和焦虑活动。多变量统计分析鉴定出20种差异显著的代谢物。进一步的代谢途径影响分析和网络分析表明，受影响的主要代谢途径包括能量代谢途径、蛋氨酸和半胱氨酸代谢途径和谷胱甘肽代谢途径。这些发现提示，BaP诱导的小脑损伤可能与代谢变化有关，并为减少BaP的负面影响提供了靶点。
Benzo(a)pyrene (BaP) is a widespread environmental contaminant that has been associated with neurotoxicity in mammals. It has strong toxic effects on the developing central nervous system. Cerebellum is associated with locomotor activity and anxiety behavior, but there is very little research about the toxic effects of BaP in cerebellum. The present study aims to investigate the global influence of BaP subacute exposure on the metabolome of rat cerebellum. Male neonatal rats (postnatal day 5) were divided into two groups: control group and BaP-treated group (2 mg/kg/day for 7 weeks). Open field test and transmission electron microscopy were performed to analyze neurobehavior and ultramicrostructure alteration. Gas chromatography-mass spectrometry (GC-MS) was used to analyze metabolites of the cerebellum in both groups. The results revealed that postnatal exposure to BaP promoted pathological changes in the cerebellum and increased locomotor and anxiety activities in early adulthood. Twenty differential significant metabolites were identified by multivariate statistical analysis. Further metabolic pathway impact analysis and network analysis suggested that the primary metabolic pathways affected included pathway involved in energy metabolism, methionine and cysteine metabolism, and glutathione metabolism. These findings suggest that BaP-induced cerebellum injury may be correlated with metabolic changes and provide an area to target to reduce the negative effects of BaP.
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影响因子：
10.4
作者：
Perera FP;Tang D;Wang S;Vishnevetsky J;Zhang B;Diaz D;Camann D;Rauh V
通讯作者：
Rauh V
影响因子：
--
作者：
Popa-Wagner A;Mitran S;Sivanesan S;Chang E;Buga AM
通讯作者：
Buga AM
DOI：
--
发表时间：
2003-02
期刊：
Alternative medicine review : a journal of clinical therapeutic
影响因子：
--
作者：
Alan L. Miller
通讯作者：
Alan L. Miller
DOI：
--
发表时间：
2010-09
期刊：
Psychiatry (Edgmont (Pa. : Township))
影响因子：
--
作者：
P. Gillig;R. Sanders
通讯作者：
P. Gillig;R. Sanders
妊娠早期宫颈阴道液的代谢物谱并不能预测自发性早产。
影响因子：
5.6
作者：
Thomas MM;Sulek K;McKenzie EJ;Jones B;Han TL;Villas-Boas SG;Kenny LC;McCowan LM;Baker PN
通讯作者：
Baker PN