title: Modulation of benzo[a]pyrene induced neurotoxicity in female mice actively immunized with a B[a]P-diphtheria toxoid conjugate.
abstract: 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.
authors.affiliation: Institute of Immunology, Centre de Recherche Public de la Santé/Laboratoire National de Santé, 20A rue Auguste Lumière, L-1950 Luxembourg, Grand-Duchy of Luxembourg.
authors.forename: Mario T
authors.initials: MT
authors.lastname: Schellenberger
authors.forename: Nathalie
authors.initials: N
authors.lastname: Grova
authors.forename: Sophie
authors.initials: S
authors.lastname: Farinelle
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Willième
authors.forename: Henri
authors.initials: H
authors.lastname: Schroeder
authors.forename: Claude P
authors.initials: CP
authors.lastname: Muller
mesh_terms: D000818:Animals; D001007:Anxiety / Q000139:chemically induced / Q000517:prevention & control / Q000523:psychology; D001564:Benzo(a)pyrene / Q000493:pharmacokinetics / Q000633:toxicity*; D001835:Body Weight / Q000187:drug effects; D001923:Brain Chemistry / Q000187:drug effects; D002851:Chromatography, High Pressure Liquid; D004168:Diphtheria Toxoid / Q000737:chemistry / Q000627:therapeutic use*; D004785:Environmental Pollutants / Q000009:adverse effects*; D005260:Female; D007114:Immunization; D000922:Immunotoxins / Q000737:chemistry / Q000627:therapeutic use*; D018782:Maze Learning / Q000187:drug effects; D008570:Memory, Short-Term / Q000187:drug effects; D051379:Mice; D008807:Mice, Inbred BALB C; D009043:Motor Activity / Q000187:drug effects; D020258:Neurotoxicity Syndromes / Q000276:immunology / Q000517:prevention & control*; D010047:Ovalbumin; D011597:Psychomotor Performance / Q000187:drug effects; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D016194:Receptors, N-Methyl-D-Aspartate / Q000096:biosynthesis
chemical_list: D004168:Diphtheria Toxoid; D004785:Environmental Pollutants; D000922:Immunotoxins; D012333:RNA, Messenger; D016194:Receptors, N-Methyl-D-Aspartate; D001564:Benzo(a)pyrene; D010047:Ovalbumin
keywords: B[a]P; B[a]P-BA; Benzo[a]pyrene; Benzo[a]pyrenyl Butyric Acid; CFA; Cyp1a1; Cyp1b1; Cytochrome P450; Cytochrome P450, family 1 subfamily B, polypeptide 1; Cytochrome P450, family 1, subfamily A, polypeptide 1; DT; IFA; Immunization; MW; N-methyl-d-aspartate; NMDA; NMDA receptor; Neurotoxicity; PAHs; RT; SE; complete Freund's adjuvant; diphtheria toxoid; incomplete Freund's adjuvant; intraperitoneal; ip; molecular weight; n.s.; not significant; polycyclic aromatic hydrocarbons; room temperature; standard error