Pb exposure prolongs the time period for postnatal transient uptake of 5-HT by murine LSO neurons.

Pb exposure prolongs the time period for postnatal transient uptake of 5-HT by murine LSO neurons.
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DOI:
10.1016/j.neuro.2016.10.010
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发表时间:
2016-12
期刊:
影响因子:
3.4
通讯作者:
Lurie DI
Lurie DI
中科院分区:
医学3区
文献类型:
--
作者:
Park S;Nevin AB;Cardozo-Pelaez F;Lurie DI

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铅暴露与认知缺陷有关,包括儿童的注意缺陷多动障碍(ADHD),并改变人类和动物的听觉时间处理。5-羟色胺与听觉时间处理有关,我们实验室以前的研究表明,发育铅降低成年小鼠外侧上级橄榄(LSO)5-羟色胺(5-HT)的表达。在发育过程中,某些非血清素能感觉神经元(包括听觉LSO神经元)通过血清素再吸收转运蛋白(SERT)短暂吸收5-HT。5-HT的摄取对于感觉系统的发育是重要的。本研究探讨了铅对出生后早期小鼠LSO内孕酮能系统的影响。小鼠暴露于中等铅(0.01mM)或高铅(0.1mM)在整个妊娠期和出生后第4天(P4)和P8。我们发现铅暴露抑制了LSO神经元5-HT的正常发育表达,这与LSO细胞体上SERT的表达有关。出生后LSO神经元5-HT表达延长与LSO内突触免疫标记减少相关。这种铅相关的突触密度下降的LSO可能有助于听觉时间处理缺陷和认知缺陷与发展铅暴露。
Pb exposure is associated with cognitive deficits including Attention Deficit Hyperactivity Disorder (ADHD) in children and alters auditory temporal processing in humans and animals. Serotonin has been implicated in auditory temporal processing and previous studies from our laboratory have demonstrated that developmental Pb decreases expression of serotonin (5-HT) in the adult murine lateral superior olive (LSO). During development, certain non-serotonergic sensory neurons, including auditory LSO neurons, transiently take up 5-HT through the serotonin reuptake transporter (SERT). The uptake of 5-HT is important for development of sensory systems. This study examines the effect of Pb on the serotonergic system in the LSO of the early postnatal mouse. Mice were exposed to moderate Pb (0.01mM) or high Pb (0.1mM) throughout gestation and postnatal day 4 (P4) and P8. We found that Pb exposure prolongs the normal developmental expression of 5-HT by LSO neurons and this is correlated with expression of SERT on LSO cell bodies. The prolonged expression of 5-HT by postnatal LSO neurons is correlated with decreased synaptic immunolabeling within the LSO. This Pb-associated decrease in synaptic density within the LSO could contribute to the auditory temporal processing deficits and cognitive deficits associated with developmental Pb exposure.