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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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Abstract

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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Funding

This report was financially supported by National Natural Science Foundation of China (Grant No. 81502777 and Grant No. 81372957).

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  1. Baijie Tu & Yinyin Xia

    Present address: Department of Occupational and Environmental Hygiene, School of Public Health and Management, Chongqing Medical University, No. 1 Yixueyuan Road, Yuzhong District, Chongqing, 400016, China

Authors and Affiliations

  1. School of Public Health and Management, Research Center for Medicine and Social Development, Innovation Center for Social Risk Governance in Health, Chongqing Medical University, Chongqing, China

    Chunlin Li, Jing Wang, Qiuping Su, Kai Yang, Chengzhi Chen, XueJun Jiang, Shuqun Cheng, Tingting Mo, Ruiyuan Zhang, Baijie Tu & Yinyin Xia

  2. The Liggins Institute, University of Auckland, Auckland, New Zealand

    Tingli Han

  3. China-Canada-New Zealand Joint Laboratory of Maternal and Fetal Medicine, Chongqing Medical University, Chongqing, China

    Tingli Han & Yinyin Xia

  4. Department of Statistics, School of Public Health and Management, Chongqing Medical University, Chongqing, China

    Bin Peng

  5. Department of Epidemiology and Biostatistics, School of Population Health, University of Queensland, Brisbane, Australia

    Yuming Guo

  6. College of Medicine, Biological Sciences and Psychology, University of Leicester, P.O. Box 138, Leicester, LE1 9HN, UK

    Philip N. Baker

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Li, C., Wang, J., Su, Q. et al. Postnatal Subacute Benzo(a)Pyrene Exposure Caused Neurobehavioral Impairment and Metabolomic Changes of Cerebellum in the Early Adulthood Period of Sprague-Dawley Rats. Neurotox Res 33, 812–823 (2018). https://doi.org/10.1007/s12640-017-9832-8

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