TY - JOUR
T1 - 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
AU - Grova, Nathalie
AU - Schroeder, Henri
AU - Farinelle, Sophie
AU - Prodhomme, Emmanuel
AU - Valley, Anne
AU - Muller, Claude P.
N1 - Funding Information:
We are grateful to Jonathan D. Turner, Laetitia Pelascini, Emilie Charpentier, Andrée Morel, Daniel Moncotel for their excellent technical assistance. We acknowledge the support of the Fond National de la Recherche (Grant FNR/01/04/11), the CRP-Santé and the Ministry of Research of Luxembourg for the continued support. This work was also supported by the Institut National de la Recherche Agronomique and the Ministère de l’Education nationale, de la Recherche et de la Technologie (France) and the International Research Training Group (Grant DFG GRK1389/1, Bonn Germany).
PY - 2008/8
Y1 - 2008/8
N2 - 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.
AB - 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.
KW - Benzo[a]pyrene
KW - Blood and brain concentrations
KW - Elevated-plus maze
KW - Hole-board apparatus
KW - NMDA glutamate receptor
KW - NR1 and NR2A/B subunits
UR - http://www.scopus.com/inward/record.url?scp=49049093593&partnerID=8YFLogxK
U2 - 10.1016/j.chemosphere.2007.12.037
DO - 10.1016/j.chemosphere.2007.12.037
M3 - Article
C2 - 18442843
AN - SCOPUS:49049093593
SN - 0045-6535
VL - 73
SP - S295-S302
JO - Chemosphere
JF - Chemosphere
IS - 1 SUPPL.
ER -