Low-level human equivalent gestational lead exposure produces sex-specific motor and coordination abnormalities and late-onset obesity in year-old mice.
Low-level human equivalent gestational lead exposure produces sex-specific motor and coordination abnormalities and late-onset obesity in year-old mice.
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DOI：
10.1289/ehp.10862
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发表时间：
2008-03
影响因子：
10.4
通讯作者：
Fox DA
中科院分区：
文献类型：
--
作者：
Leasure JL;Giddabasappa A;Chaney S;Johnson JE Jr;Pothakos K;Lau YS;Fox DA
低水平的铅暴露与儿童的认知和神经系统疾病有关。然而，妊娠期铅暴露（GLE）的长期影响很少受到关注。我们的目标是建立一个小鼠模型的人类等效GLE，并确定剂量反应的影响，体重，运动功能和多巴胺神经化学在岁的后代。我们将雌性C57 BL/6小鼠暴露于含有0、27（低）、55（中等）或109 ppm（高）铅的水中，从交配前2周开始，整个妊娠期，直到出生后第10天（PN 10）。在整个实验过程中获得母体和窝仔测量值、血铅浓度（[BPb]）和体重。运动行为的存在和不存在的安非他明，转轮活动，转棒试验，和多巴胺的利用进行了检查，在岁的小鼠。PN 0 -10时，对照组、低、中和高剂量GLE组的峰值[BPb]分别< 1、≤ 10、24-27和33-42 μg/dL。岁的雄性而不是雌性GLE小鼠表现出迟发性肥胖。同样，我们观察到雄性特异性自发运动活动减少，安非他明诱导的运动活动增加，并在一岁的GLE小鼠转棒性能下降。多巴胺及其主要代谢物的水平在一岁的雄性小鼠中发生了变化，尽管只有前脑的利用率增加。GLE诱导的变化在低剂量GLE小鼠中始终较大。我们的新结果表明，GLE产生永久性男性特异性赤字。非单调的剂量依赖性反应表明，低水平的GLE产生最不利的影响。这些数据加强了这样一种想法，即剂量反应毒物接触的终生措施应该是神经毒性风险评估过程的一个组成部分。
Low-level developmental lead exposure is linked to cognitive and neurological disorders in children. However, the long-term effects of gestational lead exposure (GLE) have received little attention. Our goals were to establish a murine model of human equivalent GLE and to determine dose–response effects on body weight, motor functions, and dopamine neurochemistry in year-old offspring. We exposed female C57BL/6 mice to water containing 0, 27 (low), 55 (moderate), or 109 ppm (high) of lead from 2 weeks prior to mating, throughout gestation, and until postnatal day 10 (PN10). Maternal and litter measures, blood lead concentrations ([BPb]), and body weights were obtained throughout the experiment. Locomotor behavior in the absence and presence of amphetamine, running wheel activity, rotarod test, and dopamine utilization were examined in year-old mice. Peak [BPb] were < 1, ≤ 10, 24–27, and 33–42 μg/dL in control, low-, moderate- and high-dose GLE groups at PN0–10, respectively. Year-old male but not female GLE mice exhibited late-onset obesity. Similarly, we observed male-specific decreased spontaneous motor activity, increased amphetamine-induced motor activity, and decreased rotarod performance in year-old GLE mice. Levels of dopamine and its major metabolite were altered in year-old male mice, although only forebrain utilization increased. GLE-induced alterations were consistently larger in low-dose GLE mice. Our novel results show that GLE produced permanent male-specific deficits. The nonmonotonic dose-dependent responses showed that low-level GLE produced the most adverse effects. These data reinforce the idea that lifetime measures of dose–response toxicant exposure should be a component of the neurotoxic risk assessment process.
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影响因子：
158.5
作者：
BAGHURST, PA;MCMICHAEL, AJ;TONG, SL
通讯作者：
TONG, SL
影响因子：
4.2
作者：
BARONE, S;STANTON, ME;MUNDY, WR
通讯作者：
MUNDY, WR
DOI：
10.1002/bdra.20311
发表时间：
2006-11-01
影响因子：
--
作者：
Correa, Adolfo;Min, Yuan-I;Jackson, Leila W.
通讯作者：
Jackson, Leila W.
美国儿童的环境有毒物质和注意力缺陷多动障碍的暴露。
影响因子：
10.4
作者：
Braun, Joe M;Kahn, Robert S;Froehlich, Tanya;Auinger, Peggy;Lanphear, Bruce P
通讯作者：
Lanphear, Bruce P
影响因子：
2.5
作者：
DOBBING, J;SANDS, J
通讯作者：
SANDS, J