title: Sub-acute administration of benzo[a]pyrene (B[a]P) reduces anxiety-related behaviour in adult mice and modulates regional expression of N-methyl-D-aspartate (NMDA) receptors genes in relevant brain regions.
abstract: Abnormal glutamatergic transmission caused by modulation of N-methyl-D-aspartate (NMDA) receptors was demonstrated in animal models chronically exposed to various organic micropollutants. Recent developments in neurobiology have implicated these receptors in the regulation of anxiety. In order to investigate anxiety-related effects of benzo[a]pyrene (B[a]P), Balb/c mice were sub-acutely exposed to B[a]P (0.02-200 mg kg(-1) day(-1), 10 days, i.p.). Their performance was tested in the elevated-plus maze and the hole-board apparatus and the NMDA receptor expression genes (NR1, 2A and 2B subunits) was measured in eight brain regions. Mice treated with 20-200 mg kg(-1) B[a]P showed a disproportionate accumulation of B[a]P and its metabolites (in particular, the toxic 7,8-diol-B[a]P) in the blood and even more in the brain. These mice were less anxious than controls in the hole-board test and the elevated-plus maze. This observation was associated with an overexpression of the NMDA NR1 receptor gene and concomitant decreases of the NR2A and NR2B subunits expression in the hippocampus, the hypothalamus and the cerebellum. In the temporal cortex, a significant dose-related decrease of NR2A was observed whereas the other subunits remained unchanged. In conclusion, a sub-acute exposure to B[a]P (20 and 200 mg kg(-1)) reduced anxiety-related behaviour in adult mice and concomitantly impaired NMDA receptor gene expression in relevant brain regions.
authors.affiliation: Institute of Immunology, Laboratoire National de Santé, 20A Rue Auguste Lumière, P.O. Box 1102, L-1011 Luxembourg, Luxembourg.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Grova
authors.forename: Henri
authors.initials: H
authors.lastname: Schroeder
authors.forename: Sophie
authors.initials: S
authors.lastname: Farinelle
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Prodhomme
authors.forename: Anne
authors.initials: A
authors.lastname: Valley
authors.forename: Claude P
authors.initials: CP
authors.lastname: Muller
mesh_terms: D000818:Animals; D001007:Anxiety / Q000139:chemically induced / Q000235:genetics / Q000503:physiopathology*; D001522:Behavior, Animal / Q000187:drug effects*; D001564:Benzo(a)pyrene / Q000008:administration & dosage / Q000378:metabolism / Q000633:toxicity*; D001921:Brain / Q000033:anatomy & histology* / Q000187:drug effects / Q000378:metabolism*; D003296:Cooking; D004305:Dose-Response Relationship, Drug; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects*; D019570:Inhalation Exposure; D051379:Mice; D016273:Occupational Exposure; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000235:genetics* / Q000378:metabolism; D012907:Smoking / Q000009:adverse effects
chemical_list: D012333:RNA, Messenger; D016194:Receptors, N-Methyl-D-Aspartate; D001564:Benzo(a)pyrene