Modulation of benzo[a]pyrene induced neurotoxicity in female mice actively immunized with a B[a]P–diphtheria toxoid conjugate

• Published in: Toxicology and applied pharmacology 2013-09, Vol.271 (2), p.175-183
• Main Authors: Schellenberger, Mario T., Grova, Nathalie, Farinelle, Sophie, Willième, Stéphanie, Schroeder, Henri, Muller, Claude P.
• Format: Article
• Language: English
• Subjects: 60 APPLIED LIFE SCIENCES; Animals; Anxiety - chemically induced; Anxiety - prevention & control; Anxiety - psychology; Bacterial diseases; Bacteriology; Benzo(a)pyrene - pharmacokinetics; Benzo(a)pyrene - toxicity; Benzo[a]pyrene; Biological and medical sciences; Body Weight - drug effects; Brain Chemistry - drug effects; BUTYRIC ACID; CARCINOGENESIS; CARCINOGENS; CEREBELLUM; Chromatography, High Pressure Liquid; Cytochrome P450; DIPHTHERIA; Diphtheria Toxoid - chemistry; Diphtheria Toxoid - therapeutic use; Ent and stomatologic bacterial diseases; Environmental Pollutants - adverse effects; Female; Fundamental and applied biological sciences. Psychology; HIPPOCAMPUS; Human bacterial diseases; Immunization; Immunotoxins - chemistry; Immunotoxins - therapeutic use; Infectious diseases; Life Sciences; Maze Learning - drug effects; Medical sciences; Memory, Short-Term - drug effects; MESSENGER-RNA; METABOLITES; MICE; Mice, Inbred BALB C; Microbiology; MOLECULAR WEIGHT; Motor Activity - drug effects; Neurotoxicity; Neurotoxicity Syndromes - immunology; Neurotoxicity Syndromes - prevention & control; NMDA receptor; Ovalbumin; Pathogenicity, virulence, toxins, bacteriocins, pyrogens, host-bacteria relations, miscellaneous strains; POLYCYCLIC AROMATIC HYDROCARBONS; POLYPEPTIDES; Psychomotor Performance - drug effects; PYRENE; Real-Time Polymerase Chain Reaction; RECEPTORS; Receptors, N-Methyl-D-Aspartate - biosynthesis; RNA, Messenger - biosynthesis; RNA, Messenger - genetics; Toxicology; VACCINES
• ISSN: 0041-008X; 1096-0333
• DOI: 10.1016/j.taap.2013.05.007

Benzo[a]pyrene (B[a]P) is a small molecular weight carcinogen and the prototype of polycyclic aromatic hydrocarbons (PAHs). While these compounds are primarily known for their carcinogenicity, B[a]P and its metabolites are also neurotoxic for mammalian species. To develop a prophylactic immune strategy against detrimental effects of B[a]P, female Balb/c mice immunized with a B[a]P–diphtheria toxoid (B[a]P–DT) conjugate vaccine were sub-acutely exposed to 2mg/kg B[a]P and behavioral performances were monitored in tests related to learning and memory, anxiety and motor coordination. mRNA expression of the NMDA receptor (NR1, 2A and 2B subunits) involved in the above behavioral functions was measured in 5 brain regions. B[a]P induced NMDA1 expression in three (hippocampus, amygdala and cerebellum) of five brain regions investigated, and modulated NMDA2 in two of the five brain regions (frontal cortex and cerebellum). Each one of these B[a]P-effects was reversed in mice that were immunized against this PAH, with measurable consequences on behavior such as anxiety, short term learning and memory. Thus active immunization against B[a]P with a B[a]P–DT conjugate vaccine had a protective effect and attenuated the pharmacological and neurotoxic effects even of high concentrations of B[a]P. •B[a]P-antibodies attenuated B[a]P induced NMDA expression in several brain regions.•B[a]P had measurable consequences on anxiety, short term learning and memory.•B[a]P immunization attenuated the pharmacological and neurotoxic effects of B[a]P.•Vaccination may also provide some protection against chemical carcinogenesis.