Preweaning manganese exposure causes hyperactivity, disinhibition, and spatial learning and memory deficits associated with altered dopamine receptor and transporter levels.
Preweaning manganese exposure causes hyperactivity, disinhibition, and spatial learning and memory deficits associated with altered dopamine receptor and transporter levels.
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DOI：
10.1002/syn.20736
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发表时间：
2010-05
期刊：
影响因子：
2.3
通讯作者：
Smith, Donald R.
中科院分区：
文献类型：
--
作者：
Kern, Cynthia H.;Stanwood, Gregg D.;Smith, Donald R.
儿童流行病学研究报告了膳食锰（Mn）暴露升高与神经行为和神经认知缺陷之间的关联。为了更好地理解早期锰暴露与神经行为缺陷之间的关系，我们在出生后第1 - 21天（PND）以0、25或50 mg Mn/kg/d的剂量经口给予新生大鼠，并使用开放式竞技场（PND 23）、高架十字迷宫（PND 23）和8臂放射状迷宫（PND 33-46）范式评估行为表现。在PND 24测定脑多巴胺D1和D2样受体和DAT转运蛋白密度，并测量血液和脑Mn水平以与行为测试一致（PND 24，PND 36）。断奶前锰暴露引起多动和行为抑制的开放竞技场，但没有改变的行为在高架十字迷宫。与对照组相比，锰暴露的男性在桡臂迷宫中犯了更多的参考错误和更多的工作错误。较少的锰暴露的男性达到径向迷宫学习标准，他们需要更多的会话天，以达到与对照组相比。锰暴露的动物也表现出更大的频率刻板反应策略在迷宫中寻找诱饵武器。这些行为和学习缺陷与多巴胺D1和D2受体和多巴胺转运蛋白在前额叶皮层，背侧纹状体核，和背侧纹状体的表达改变。这些数据证实了流行病学研究的儿童，并表明，暴露于锰在神经发育过程中显着改变多巴胺能突触环境中的脑核，介导控制的执行功能行为，如反应性和认知灵活性。
Epidemiological studies in children have reported associations between elevated dietary manganese (Mn) exposure and neurobehavioral and neurocognitive deficits. To better understand the relationship between early Mn exposure and neurobehavioral deficits, we treated neonate rats with oral Mn doses of 0, 25, or 50 mg Mn/kg/d over postnatal day (PND) 1 – 21, and evaluated behavioral performance using open arena (PND 23), elevated plus maze (PND 23), and 8-arm radial maze (PND 33–46) paradigms. Brain dopamine D1 and D2-like receptors, and DAT transporter densities were determined on PND 24, and blood and brain Mn levels were measured to coincide with behavioral testing (PND 24, PND 36). Pre-weaning Mn exposure caused hyperactivity and behavioral disinhibition in the open arena, but no altered behavior in the elevated plus maze. Manganese-exposed males committed significantly more reference and marginally more working errors in the radial arm maze compared to controls. Fewer Mn exposed males achieved the radial maze learning criterion, and they required more session days to reach it compared to controls. Manganese-exposed animals also exhibited a greater frequency of stereotypic response strategy in searching for the baited arms in the maze. These behavioral and learning deficits were associated with altered expression of the dopamine D1 and D2 receptors and the dopamine transporter in prefrontal cortex, nucleus accumbens, and dorsal striatum. These data corroborate epidemiological studies in children, and suggest that exposure to Mn during neurodevelopment significantly alters dopaminergic synaptic environments in brain nuclei that mediate control of executive function behaviors, such as reactivity and cognitive flexibility.
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DOI：
10.1038/sj.jea.7500412
发表时间：
2005-07-01
期刊：
JOURNAL OF EXPOSURE ANALYSIS AND ENVIRONMENTAL EPIDEMIOLOGY
影响因子：
--
作者：
Arcus-Arth, A;Krowech, G;Zeise, L
通讯作者：
Zeise, L
影响因子：
5.3
作者：
Carr, DB;O'Donnell, P;Sesack, SR
通讯作者：
Sesack, SR
影响因子：
4.7
作者：
CHANDRA, SV;SHUKLA, GS;SAXENA, DK
通讯作者：
SAXENA, DK
影响因子：
2.7
作者：
Ducottet, C;Belzung, C
通讯作者：
Belzung, C
影响因子：
3.8
作者：
Dorman, DC;McElveen, AM;Wong, BA
通讯作者：
Wong, BA