Low-level human equivalent gestational lead exposure produces supernormal scotopic electroretinograms, increased retinal neurogenesis, and decreased retinal dopamine utilization in rats.
Low-level human equivalent gestational lead exposure produces supernormal scotopic electroretinograms, increased retinal neurogenesis, and decreased retinal dopamine utilization in rats.
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DOI：
10.1289/ehp.11268
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发表时间：
2008-05
影响因子：
10.4
通讯作者：
O'Callaghan JP
中科院分区：
文献类型：
--
作者：
Fox DA;Kala SV;Hamilton WR;Johnson JE;O'Callaghan JP
儿童和动物出生后铅暴露会产生视觉系统的改变，主要表现为视杆介导的视网膜电图（ERG）振幅（亚正常）下降。相反，低水平妊娠期铅暴露（GLE）会增加儿童暗位erg的振幅（异常）。本研究的目的是建立一个人类等效GLE的大鼠模型，并确定剂量-反应对暗位ERGs和成年后代视网膜形态、生物化学和多巴胺代谢的影响。我们从交配前2周开始，将雌性龙-埃文斯戴帽大鼠暴露于含铅量为0,27（低），55（中）或109（高）ppm的水中，贯穿整个妊娠期，直到出生后（PND） 10。我们测量了产妇和产仔指数、血铅浓度（BPb）、视网膜铅浓度、锌浓度和体重。在PND90上进行视网膜实验。在PNDs 0 ~ 10时，对照组、低GLE组、中GLE组和高GLE组的峰值浓度分别< 1、12、24和46 μg/dL。低、中度GLE患者出现ERG异常，杆状光感受器和杆状双极细胞神经发生增加。相反，高水平GLE导致ERG亚正常，杆状细胞丢失，视网膜锌水平降低。GLE产生多巴胺及其利用的剂量依赖性降低。低和中等水平的GLE由于杆状信号通路中细胞的神经发生增加和/或多巴胺利用减少而产生持续的暗位ERG异常，而高水平的GLE产生以ERG亚正常为特征的杆状选择性毒性。ERG是GLE的鉴别和非侵入性生物标志物。倒u型剂量反应曲线显示了发育中的视网膜对GLE的敏感性和脆弱性。
Postnatal lead exposure in children and animals produces alterations in the visual system primarily characterized by decreases in the rod-mediated (scotopic) electroretinogram (ERG) amplitude (subnormality). In contrast, low-level gestational Pb exposure (GLE) increases the amplitude of scotopic ERGs in children (supernormality). The goal of this study was to establish a rat model of human equivalent GLE and to determine dose–response effects on scotopic ERGs and on retinal morphology, biochemistry, and dopamine metabolism in adult offspring. We exposed female Long-Evans hooded rats to water containing 0, 27 (low), 55 (moderate), or 109 (high) ppm of Pb beginning 2 weeks before mating, throughout gestation, and until postnatal day (PND) 10. We measured maternal and litter indices, blood Pb concentrations (BPb), retinal Pb concentrations, zinc concentrations, and body weights. On PND90, we performed the retinal experiments. Peak BPb concentrations were < 1, 12, 24, and 46 μg/dL in control, low-, moderate- and high-level GLE groups, respectively, at PNDs 0–10. ERG supernormality and an increased rod photoreceptor and rod bipolar cell neurogenesis occurred with low- and moderate-level GLE. In contrast, high-level GLE produced ERG subnormality, rod cell loss, and decreased retinal Zn levels. GLE produced dose-dependent decreases in dopamine and its utilization. Low- and moderate-level GLE produced persistent scotopic ERG supernormality due to an increased neurogenesis of cells in the rod signaling pathway and/or decreased dopamine utilization, whereas high-level GLE produced rod-selective toxicity characterized by ERG subnormality. The ERG is a differential and noninvasive biomarker of GLE. The inverted U-shaped dose–response curves reveal the sensitivity and vulnerability of the developing retina to GLE.
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影响因子：
15.9
作者：
BODISWOLLNER, I
通讯作者：
BODISWOLLNER, I
影响因子：
3.4
作者：
FOX, DA;CHU, LWF
通讯作者：
CHU, LWF
DOI：
10.1016/j.ijdevneu.2005.07.005
发表时间：
2005-11-01
影响因子：
1.8
作者：
Jaako-Movits, K;Zharkovsky, T;Zharkovsky, A
通讯作者：
Zharkovsky, A
影响因子：
4.8
作者：
He, LH;Poblenz, AT;Fox, DA
通讯作者：
Fox, DA
影响因子：
2.5
作者：
DOBBING, J;SANDS, J
通讯作者：
SANDS, J