Down-regulation of early ionotrophic glutamate receptor subunit developmental expression as a mechanism for observed plasticity deficits following gestational exposure to benzo(a)pyrene.

摘要: The focus of this study was to characterize the impact gestational exposure benzo(a)pyrene [B(a)P] on modulation glutamate receptor subunit expression that is critical for maintenance synaptic plasticity mechanisms during hippocampal or cortical development in offspring. Previous studies have demonstrated and/or (as measured by long-term potentiation and S1-cortex spontaneous/evoked neuronal activity) learning behavior fixed-ratio performance operant testing) significantly impaired polycyclic aromatic halogenated hydrocarbon-exposed offspring as compared controls. These previous also revealed brain body weight ratios are greater exposed relative controls indicative intrauterine growth retardation which has been shown manifest low birth Recent epidemiological identified an effect prenatal airborne hydrocarbons neurodevelopment first 3 years life among inner-city children [Perera FP, Rauh V, Whyatt RM, Tsai WY, Tang D, Diaz et al. Effect children. Environ Health Perspect 2006;114:1287-92]. present utilizes a well-characterized animal model test hypothesis B(a)P causes dysregulation developmental ionotropic expression, namely N-methyl-d-aspartate (NMDAR) alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionate (AMPAR) both mechanisms. To mechanistically ascertain basis B(a)P-induced perturbations, timed pregnant Long-Evans rats were oral subacute regimen 0, 25 150mug/kg BW gestation days 14-17. sub-hypothesis tested whether would result significant disposition second down-regulation early NMDA AMPA subunits hippocampus well primary cultures. results these significant: (1) cortex, (2) mRNA protein (3) voltage-dependent decreases amplitude inward currents at negative potentials B(a)P-treated membranes. suggest behavioral deficits produced least, part, function time when excitatory synapses being formed developing central nervous system. predict B(a)P-exposed with reduced parallel deficit behaviors depend normal functioning will be observed throughout life.