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The potent neurotoxicity of benzo[a]pyrene (B[a]P) has been suggested to be a susceptibility factor accelerating the onset of brain tumours and the emergence of neurobehavioural disturbances. B[a]P has been shown to be neurotoxic, acting directly on both the central and peripheral nervous systems, as well as indirectly via peripheral organs like liver and gut. By using a realistic B[a]P exposure scenario (0.02–200 mg/kg/day, 10 days) in mice, we elucidated brain-specific B[a]P metabolism and at identified hydroxylated B[a]P metabolites in serum which could be used as markers of cognitive impairment. Repeated oral administration of B[a]P led to, at the doses of 20 and 200 mg/kg/day, significant overexpression of Cyp1a1/Cyp1b1 in 2 out of the 3 brain regions considered, thereby suggesting the ability of the brain to metabolize B[a]P itself. At the same doses, mice exhibited a reduction in anxiety in both the elevated plus maze and the hole board apparatus. Concomitantly, B[a]P triggered dose-dependent changes in Nmda subunit expression (Nr1 and Nr2a/Nr2b) in areas involved in cognition. We detected 9-OH-B[a]P and 7,8-diol-B[a]P in serum at the level for which cognitive impairment was observed. We suggest that these metabolites may, in the future be exploited as potent biomarkers of B[a]P-induced cognitive impairments.
Lynda Cherif; Lei Cao-Lei; Sophie Farinelle; Claude Muller; Jonathan Turner; Henri Schroeder; Nathalie Grova. Assessment of 9-OH- and 7,8-diol-benzo[a]pyrene in Blood as Potent Markers of Cognitive Impairment Related to benzo[a]pyrene Exposure: An Animal Model Study. Toxics 2021, 9, 50 .
AMA StyleLynda Cherif, Lei Cao-Lei, Sophie Farinelle, Claude Muller, Jonathan Turner, Henri Schroeder, Nathalie Grova. Assessment of 9-OH- and 7,8-diol-benzo[a]pyrene in Blood as Potent Markers of Cognitive Impairment Related to benzo[a]pyrene Exposure: An Animal Model Study. Toxics. 2021; 9 (3):50.
Chicago/Turabian StyleLynda Cherif; Lei Cao-Lei; Sophie Farinelle; Claude Muller; Jonathan Turner; Henri Schroeder; Nathalie Grova. 2021. "Assessment of 9-OH- and 7,8-diol-benzo[a]pyrene in Blood as Potent Markers of Cognitive Impairment Related to benzo[a]pyrene Exposure: An Animal Model Study." Toxics 9, no. 3: 50.
In utero exposure to environmental stress in both animals and humans could result in long-term epigenome alterations and which further lead to consequences for adaptation and development in the offspring. Epigenetics, especially DNA methylation, is considered one of the most widely studied and well-characterized mechanisms involved in the long-lasting effects of in utero stress exposure. In this review, we outlined evidence from animal and human prenatal research supporting the view that prenatal stress could lead to lasting, broad and functionally organized signatures in DNA methylation which, in turn, could mediate exposure-phenotype associations. We also emphasized the advantage of using stressor from quasi-randomly assigned experiments. Furthermore, we discuss challenges that still need to be addressed in this field in the futur
L. Cao-Lei; S.R. de Rooij; S. King; S.G. Matthews; G.A.S. Metz; T.J. Roseboom; M. Szyf. Prenatal stress and epigenetics. Neuroscience & Biobehavioral Reviews 2020, 117, 198 -210.
AMA StyleL. Cao-Lei, S.R. de Rooij, S. King, S.G. Matthews, G.A.S. Metz, T.J. Roseboom, M. Szyf. Prenatal stress and epigenetics. Neuroscience & Biobehavioral Reviews. 2020; 117 ():198-210.
Chicago/Turabian StyleL. Cao-Lei; S.R. de Rooij; S. King; S.G. Matthews; G.A.S. Metz; T.J. Roseboom; M. Szyf. 2020. "Prenatal stress and epigenetics." Neuroscience & Biobehavioral Reviews 117, no. : 198-210.
Exposure to stress during pregnancy may program susceptibility to the development of obesity in offspring. Our goal was to determine whether prenatal maternal stress (PNMS) due to a natural disaster was associated with child obesity, and to compare the DNA methylation profiles in obese versus non-obese children at age 13½ years. Women and their children were involved in the longitudinal natural disaster study-Project Ice Strom, which served as a human model to study PNMS. Blood was collected from 31 children (including five obese children). Infinium HumanMethylation450 BeadChip Array was performed for genome-wide DNA methylation analyses. Results demonstrated a well-defined obesity-associated genome-wide DNA methylation pattern. There were 277 CpGs, corresponding to 143 genes, were differentially-methylated. IPA analyses revealed 51 canonical pathways, and enrichment of pathways was involved in immune function. Although no significant association was found between PNMS and child obesity, the preliminary data in the study revealed obesity-associated methylation patterns on a genome-wide level in children.
Lei Cao-Lei; Guillaume Elgbeili; Moshe Szyf; David P. Laplante; Suzanne King. Differential genome-wide DNA methylation patterns in childhood obesity. BMC Research Notes 2019, 12, 174 .
AMA StyleLei Cao-Lei, Guillaume Elgbeili, Moshe Szyf, David P. Laplante, Suzanne King. Differential genome-wide DNA methylation patterns in childhood obesity. BMC Research Notes. 2019; 12 (1):174.
Chicago/Turabian StyleLei Cao-Lei; Guillaume Elgbeili; Moshe Szyf; David P. Laplante; Suzanne King. 2019. "Differential genome-wide DNA methylation patterns in childhood obesity." BMC Research Notes 12, no. 1: 174.