Chronic administration of Benzo(a)pyrene induces memory impairment and anxiety-like behavior and increases of NR2B DNA methylation

Wenping Zhang, Fengjie Tian, Jinping Zheng, Senlin Li, Mei Qiang

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

Background: Recently, an increasing number of human and animal studies have reported that exposure to benzo(a)pyrene (BaP) induces neurological abnormalities and is also associated with adverse effects, such as tumor formation, immunosuppression, teratogenicity, and hormonal disorders. However, the exact mechanisms underlying BaP-induced impairment of neurological function remain unclear. The aim of this study was to examine the regulating mechanisms underlying the impact of chronic BaP exposure on neurobehavioral performance. Methods: C57BL mice received either BaP in different doses (1.0, 2.5, 6.25 mg/kg) or olive oil twice a week for 90 days. Memory and emotional behaviors were evaluated using Y-maze and open-field tests, respectively. Furthermore, levels of mRNA expression were measured by using qPCR, and DNA methylation of NMDA receptor 2B subunit (NR2B) was examined using bisulfate pyrosequencing in the prefrontal cortex and hippocampus. Results: Compared to controls, mice that received BaP (2.5, 6.25 mg/kg) showed deficits in shortterm memory and an anxiety-like behavior. These behavioral alterations were associated with a down-regulation of the NR2B gene and a concomitant increase in the level of DNA methylation in the NR2B promoter in the two brain regions. Conclusions: Chronic BaP exposure induces an increase in DNA methylation in the NR2B gene promoter and down-regulates NR2B expression, which may contribute to its neurotoxic effects on behavioral performance. The results suggest that NR2B vulnerability represents a target for environmental toxicants in the brain.

Original languageEnglish (US)
Article numbere0149574
JournalPLoS One
Volume11
Issue number2
DOIs
StatePublished - Feb 1 2016

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Benzo(a)pyrene
DNA methylation
DNA Methylation
anxiety
Anxiety
Data storage equipment
receptors
chronic exposure
Brain
Down-Regulation
Genes
promoter regions
teratogenicity
brain
immunosuppression
mice
hippocampus
Prefrontal Cortex
toxic substances
Inbred C57BL Mouse

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Chronic administration of Benzo(a)pyrene induces memory impairment and anxiety-like behavior and increases of NR2B DNA methylation. / Zhang, Wenping; Tian, Fengjie; Zheng, Jinping; Li, Senlin; Qiang, Mei.

In: PLoS One, Vol. 11, No. 2, e0149574, 01.02.2016.

Research output: Contribution to journalArticle

Zhang, Wenping ; Tian, Fengjie ; Zheng, Jinping ; Li, Senlin ; Qiang, Mei. / Chronic administration of Benzo(a)pyrene induces memory impairment and anxiety-like behavior and increases of NR2B DNA methylation. In: PLoS One. 2016 ; Vol. 11, No. 2.
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