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Cited by 49Toxic Organic Pollutants ImpactEpigenetics and DNA MethylationCarcinogens and Genotoxicity Assessment

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

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Zhang, Wenping, Tian, Fengjie, Zheng, Jinping, Li, Senlin, Qiang, Mei·2016·PLOS ONE
DOI 10.1371/journal.pone.0149574PMC PMC4768874
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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 short-term 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.

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  • PAHs and PCBs activate mitochondria-mediated apoptotic pathways, compromising neuronal survival.

    “PAHs and PCBs activate mitochondria-mediated apoptotic pathways, thereby further compromising neuronal survival (Zhang et al., 2016).”

    From Environmental endocrine disruptors at the synapse: mechanisms linking chemical exposure to cognitive and behavioral dysfunction (2026) · cites this paper as Zhang et al., 2016

    The Introduction discusses BaP-related neurological impairment and notes that NMDA receptors are sensitive to PAHs and PCBs. The Discussion instead focuses on NR2B expression and says the mechanism of BaP neurotoxicity remains unknown. A search for mitochondrial apoptosis and neuronal survival found no passage supporting the pathway attributed to this paper. (LLM, conf=0.76)

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Authors
Zhang, W., Tian, F., Zheng, J., Li, S., & Qiang, M.
Affiliations
  • Shanxi Medical University (CN)
  • The University of Texas at San Antonio Health Science Center (US)
Corresponding author
Qiang, Mei
ORCID
Venue
PLOS ONE
Publisher
Public Library of Science (PLoS)
Published
2016-02-22
Volume
11
Issue
2
Pages
e0149574
ISSN
1932-6203 (ISSN-L)
DOI
10.1371/journal.pone.0149574
PMC
PMC4768874
OpenAlex
W2337648208
Cited by
49
References
0
Citations by year
2026: 4 · 2025: 5 · 2024: 7 · 2023: 5 · 2022: 4 · 2021: 6 · 2020: 8 · 2019: 6 · 2018: 1 · 2017: 2 · 2016: 1
FWCI
2.09
Type
journal article
Language
en
Update notices
correction (2024-12-05)
Open access
Licence
Locations
  • PLoS ONE (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • Shanxi Scholarship Council of China (2015-051)
  • Shanxi Medical University
Topics
  • Physical Sciences › Environmental Science › Health, Toxicology and Mutagenesis › Toxic Organic Pollutants Impact
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Carcinogens and Genotoxicity Assessment
Keywords
benzo[a]pyrene, long-term exposure, neurotoxicity, memory impairment, anxiety-like behavior, NR2B, NMDA receptor, DNA methylation, promoter methylation, prefrontal cortex, hippocampus, environmental toxins, neurobehavioral deficits
MeSH terms
Animals, Anxiety, Behavior, Animal, Benzo(a)pyrene, Hippocampus, Humans, Male, Memory Disorders, Receptors, N-Methyl-D-Aspartate, Prefrontal Cortex, DNA Methylation, Mice

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