期刊
NEUROTOXICOLOGY
卷 29, 期 5, 页码 846-854出版社
ELSEVIER
DOI: 10.1016/j.neuro.2008.07.008
关键词
Polycyclic aromatic hydrocarbon-(PAH); Benzo(a)pyrene-B(a)P; World Trade Center (WTC); Small for gestational age (SGA); Intrauterine growth restriction (IUGR); Bailey Scales of Infant Development (BSID-II); Susceptibility-exposure paradigm; Somatosensory cortex-S1 cortex; Cortical neuronal activity and behavior; Alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA); N-methyl-D-aspartate (NMDA); Environmental aryl hydrocarbon receptor agonists-eAhR agonist; Developmental neurotoxicity
资金
- NCI NIH HHS [U54 CA091408, R03CA130112-01, U54 CA091408-07, R03 CA130112] Funding Source: Medline
- NCRR NIH HHS [G12 RR003032-208103, G12 RR003032-21, G12 RR003032] Funding Source: Medline
- NIDA NIH HHS [R01 DA026947] Funding Source: Medline
- NIEHS NIH HHS [S11 ES014156-04, S11 ES014156-040004, S11ES014156-02, S11 ES014156-049001, S11 ES014156] Funding Source: Medline
- NIGMS NIH HHS [R25 GM059994-10, R25 GM059994, S06 GM008037, S06GM08037] Funding Source: Medline
- NIMHD NIH HHS [U54 MD007593] Funding Source: Medline
- NIMH NIH HHS [R25 MH063306-03, R24 MH057067-07, T32MH065782, R24 MH057067-03, R25 MH063306-02, T32 MH065782] Funding Source: Medline
- NINDS NIH HHS [U54 NS041071, U54 NS041071-06, R01 NS071122, U54NS041071-0002] Funding Source: Medline
- PHS HHS [G12RRO3032] Funding Source: Medline
Prenatal exposure to environmental contaminants, such as benzo(a)pyrene [B(a)P] has been shown to impair brain development. The overarching hypothesis of our work is that glutamate receptor subunit expression is crucial for cortical evoked responses and that prenatal B(a)P exposure modulates the temporal developmental expression of glutamatergic receptor Subunits in the somatosensory cortex. To characterize prenatal B(a)P exposure on the development of cortical function, pregnant Long Evans rats were exposed to low-level B(a)P (300 mu g/kg BW) by oral gavage on gestational days 14-17. At this exposure dose, there was no significant effect of B(a)P on (I) the number of pups born per litter, (2) the pre-weaning growth curves and (3) initial and final brain to body weight ratios. Control and B(a)P-exposed offspring were profiled for B(a)P metabolites in plasma and whole brain during the pre-weaning period. No detectable levels of metabolites were found in the control offspring. However, a time-dependent decrease in total metabolite concentration was observed in B(a)P-exposed offspring. On PND100-120, cerebrocortical mRNA expression was determined for the glutamatergic NMDA receptor subunit (NR2B) in control and B(a)P-exposed offspring. Neural activity was also recorded from neurons in primary somatic sensory (barrel) cortex. Semiquantitative PCR from B(a)P-exposed offspring revealed a significant 50% reduction in NR2B mRNA expression in B(a)P-exposed offspring relative to controls. Recordings from B(a)P-exposed offspring revealed that N-methyl-D-aspartate (NMDA) receptor-dependent neuronal activity in barrel cortex evoked by whisker stimulation was also significantly reduced (70%) as compared to controls. Analysis showed that the greatest deficit in cortical neuronal responses occurred in the shorter latency epochs from 5 to 20 MS post-stimulus. The results suggest that in utero exposure to benzo(a)pyrene results in diminished mRNA expression of the NMDA NR2B receptor subunit to result in late life deficits in cortical neuronal activity in the offspring. The findings from this study lead to a strong prediction that in utero exposure to benzo(a)pyrene at a time when synapses are first formed and adjusted in strength by activity in the sensory pathways will produce a strong negative effect on brain function in offspring progeny. (C) 2008 Elsevier Inc. All rights reserved.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据