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Integrated epigenetics, transcriptomics, and metabolomics to analyze the mechanisms of Benzo[a]pyrene neurotoxicity in the hippocampus.

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posted on 01.05.2019, 10:28 by J Wang, C-L Li, B-J Tu, K Yang, T-T Mo, R-Y Zhang, S-Q Cheng, C-Z Chen, X-J Jiang, T-L Han, B Peng, PN Baker, Y-Y Xia
Benzo[a]pyrene (B[a]P) is a common environmental pollutant that is neurotoxic to mammals, which can cause changes to hippocampal function and result in cognitive disorders. The mechanisms of B[a]P-induced impairments are complex. To date there have been no studies on the association of epigenetic, transcriptomic and metabolomic changes with neurotoxicity after B[a]P exposure. In the present study, we investigated the global effect of B[a]P on DNA methylation patterns, non-coding RNAs (ncRNAs) expression, coding RNAs expression, and metabolites in the rat hippocampus. Male Sprague-Dawley rats (SD rats) received daily gavage of B[a]P (2.0 mg/kg body weight [BW]) or corn oil for seven weeks. Learning and memory ability was analysed using the Morris Water Maze (MWM) test and change to cellular ultrastructure in the hippocampus was analysed using electron microscope observation. Integrated analysis of epigenetics, transcriptomics, and metabolomics was conducted to investigate the effect of B[a]P exposure on the signaling and metabolic pathways. Our results suggest that B[a]P could lead to learning and memory deficits, likely as a result of epigenetic and transcriptomic changes that further affected the expression of CACNA1C, Tpo, etc. The changes in expression ultimately affecting LTP, tyrosine metabolism and other important metabolic pathways.

Funding

This study was supported by the National Natural Science Foundation of China (No. 81502777, 81372957, 81602820, 81703187), the Natural Science Foundation Project of CQ CSTC (2015jcyjA10032, cstc2016jcyjA0223, cstc2016jcyjA0435), the Science-Technology Research Program of the CQ Municipal Commission of Education (KJ1600204), the China State Scholarship Fund, and the 111 Project.

History

Citation

Toxicological Sciences, 2018, 166(1), pp. 65–81

Author affiliation

/Organisation/COLLEGE OF LIFE SCIENCES

Version

AM (Accepted Manuscript)

Published in

Toxicological Sciences

Publisher

Oxford University Press (OUP) for Society of Toxicology

eissn

1096-0929

Acceptance date

04/06/2018

Copyright date

2018

Available date

31/07/2019

Publisher version

https://academic.oup.com/toxsci/article/166/1/65/5062621

Notes

The file associated with this record is under embargo until 12 months after publication, in accordance with the publisher's self-archiving policy. The full text may be available through the publisher links provided above.

Language

en