title: Chronic Administration of Benzo(a)pyrene Induces Memory Impairment and Anxiety-Like Behavior and Increases of NR2B DNA Methylation.
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.
authors.affiliation: Department of Neurotoxicology, School of Public Health, Shanxi Medical University, Shanxi, Taiyuan, 030001, China.
authors.forename: Wenping
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Department of Neurotoxicology, School of Public Health, Shanxi Medical University, Shanxi, Taiyuan, 030001, China.
authors.forename: Fengjie
authors.initials: F
authors.lastname: Tian
authors.affiliation: Department of Neurotoxicology, School of Public Health, Shanxi Medical University, Shanxi, Taiyuan, 030001, China.
authors.forename: Jinping
authors.initials: J
authors.lastname: Zheng
authors.affiliation: Department of Medicine, The University of Texas Health Science Center at San Antonio, San Antonio, TX, 78229, United States of America.
authors.forename: Senlin
authors.initials: S
authors.lastname: Li
authors.affiliation: Department of Children and Adolescences, School of Public Health, Shanxi Medical University, Shanxi, Taiyuan, 030001, China.
authors.forename: Mei
authors.initials: M
authors.lastname: Qiang
mesh_terms: D000818:Animals; D001007:Anxiety / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D001522:Behavior, Animal / Q000187:drug effects*; D001564:Benzo(a)pyrene / Q000633:toxicity*; D019175:DNA Methylation / Q000187:drug effects*; D006624:Hippocampus / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D006801:Humans; D008297:Male; D008569:Memory Disorders / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D051379:Mice; D017397:Prefrontal Cortex / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism*
chemical_list: C121001:NR2B NMDA receptor; D016194:Receptors, N-Methyl-D-Aspartate; D001564:Benzo(a)pyrene