Alterations in central nervous system serotonergic and dopaminergic synaptic activity in adulthood after prenatal or neonatal chlorpyrifos exposure.
Alterations in central nervous system serotonergic and dopaminergic synaptic activity in adulthood after prenatal or neonatal chlorpyrifos exposure.
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中枢神经系统血清素能和多巴胺能突触活性在产前或新生儿毒性菌暴露后成年。
DOI：
10.1289/ehp.7968
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发表时间：
2005-08
影响因子：
10.4
通讯作者：
中科院分区：
文献类型：
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作者：
暴露于毒死蜱（CPF）改变5-羟色胺（5 HT）和多巴胺系统的神经元发育，我们最近发现长期的行为改变与5 HT功能。为了表征这些效应背后的突触机制，我们将发育中的大鼠暴露于低于全身毒性阈值的CPF方案，在三个治疗窗口：妊娠天数（GD）17-20，出生后天数（PN）1-4或PN 11 - 1 - 4。在成年早期（PN 60），我们评估了包含主要5-HT和多巴胺投射的脑区的基础神经递质含量和突触活性（营业额）。CPF暴露GD 17 -20或PN 1 -4引起多个区域5 HT周转率的长期增加;这种影响并不继发于神经递质含量的变化，神经递质含量不受影响甚至下降。当治疗窗转移至PN 11 -14时，无长期效应。多巴胺周转率也显示出显着增加CPF暴露后GD 17 -20，但只有当剂量提高到明显的毒性阈值以上，然而，海马多巴胺含量显着低于正常暴露后低于或高于急性毒性阈值，表明彻底的神经毒性。这些结果表明，在一个关键的发展时期，显然无毒暴露于CPF产生持久的激活5 HT系统与5 HT相关的行为异常。
Exposure to chlorpyrifos (CPF) alters neuronal development of serotonin (5HT) and dopamine systems, and we recently found long-term alterations in behaviors related to 5HT function. To characterize the synaptic mechanisms underlying these effects, we exposed developing rats to CPF regimens below the threshold for systemic toxicity, in three treatment windows: gestational days (GD) 17–20, postnatal days (PN) 1–4, or PN11–14. In early adulthood (PN60), we assessed basal neurotransmitter content and synaptic activity (turnover) in brain regions containing the major 5HT and dopamine projections. CPF exposure on GD17–20 or PN1–4 evoked long-term increases in 5HT turnover across multiple regions; the effects were not secondary to changes in neurotransmitter content, which was unaffected or even decreased. When the treatment window was shifted to PN11–14, there were no long-term effects. Dopamine turnover also showed significant increases after CPF exposure on GD17–20, but only when the dose was raised above the threshold for overt toxicity; however, hippocampal dopamine content was profoundly subnormal after exposures below or above the acute, toxic threshold, suggesting outright neurotoxicity. These results indicate that, in a critical developmental period, apparently nontoxic exposures to CPF produce lasting activation of 5HT systems in association with 5HT-associated behavioral anomalies.