Neurochemical changes following a single dose of polybrominated diphenyl ether 47 in mice

Neurochemical changes following a single dose of polybrominated diphenyl ether 47 in mice
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DOI:
10.3109/01480545.2010.536768
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发表时间:
2011-04-01
影响因子:
2.6
通讯作者:
Herr, David W.
Herr, David W.
中科院分区:
医学4区
文献类型:
--
作者:
Gee, Jillian R.;Moser, Virginia C.;Herr, David W.

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多溴联苯醚(PBDEs)通常用作各种产品的商业阻燃剂,包括塑料和纺织品。我们实验室和文献中的先前研究表明,在大脑发育的关键时期暴露于特定的PBDE同系物(PBDE 47)可能会导致成年期发育迟缓和过度活跃。迄今为止,这些行为改变的根本原因尚不清楚,尽管体外研究将多溴二苯醚与神经递质水平的潜在改变联系起来,特别是乙酰胆碱和多巴胺。在啮齿动物和人类的多动症病例中也注意到DA功能的改变。目前的研究检查了雄性小鼠在出生后第10天急性暴露于玉米油载体或PBDE 47(1、10或30毫克/千克)的单胺水平。在PND 15、PND 20和成年期(131-159日龄)处死动物。分离皮质、纹状体和小脑并通过高效液相色谱法进行分析,以确定每个大脑区域内单胺的浓度。无论年龄大小,大脑皮层中的多巴胺水平都出现了统计学上的显著增加,但仅在10毫克/千克多溴二苯醚处理组中出现了这种情况。虽然这些效应未显示出单调的剂量反应,但我们先前报告了相同剂量组中同窝仔的活动过度,但在较低或较高剂量下未报告。因此,早期发育暴露于PBDE 47改变了雄性小鼠皮质DA的水平,这可能与同窝出生的小鼠的行为观察有关。
Polybrominated diphenyl ethers (PBDEs) are commonly used as commercial flame retardants in a variety of products, including plastics and textiles. Previous studies in our laboratory, and in the literature, showed that exposure to a specific PBDE congener (PBDE 47) during a critical period of brain development may lead to developmental delays and hyperactivity in adulthood. To date, the underlying causes of these behavioral alterations are unknown, although in vitro studies linked PBDEs with potential alterations in neurotransmitter levels, particularly acetylcholine (ACh) and dopamine (DA). Alterations in DA function have also been noted in cases of hyperactivity in rodents and humans. The current study examined monoamine levels in male mice acutely exposed to corn oil vehicle or PBDE 47 (1, 10, or 30 mg/kg) on postnatal day (PND) 10. Animals were sacrificed on PND 15, PND 20, and in adulthood (131-159 days old). The cortex, striatum, and cerebellum were isolated and analyzed by high-performance liquid chromatography to determine the concentration of monoamines within each brain region. A statistically significant increase in DA levels was seen within the cortex, regardless of age, but only in the 10-mg/kg PBDE treatment group. While these effects did not show a monotonic dose response, we previously reported hyperactivity in littermates in the same dose group, but not at the lower or higher dose. Thus, early developmental exposure to PBDE 47 alters the levels of cortical DA in male mice, which may correlate with behavioral observations in littermates.