Evaluation of multi-well microelectrode arrays for neurotoxicity screening using a chemical training set.
Evaluation of multi-well microelectrode arrays for neurotoxicity screening using a chemical training set.
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DOI：
10.1016/j.neuro.2012.05.001
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发表时间：
2012-10
期刊：
影响因子：
3.4
通讯作者：
Shafer, Timothy J.
中科院分区：
文献类型：
--
作者：
McConnell, Emma R.;McClain, Maxine A.;Ross, James;LeFew, William R.;Shafer, Timothy J.
微电极阵列(MEA)方法已被提出作为一种工具来检测暴露于药物、化学物质或颗粒的电兴奋细胞(包括神经元)的功能变化。然而，传统的单孔MEA系统缺乏筛选大量未表征化合物所需的吞吐量。最近，多井MEA(MwMEA)格式已变得可用来满足增加产量的需要。目前的实验检测了一组30种化学物质对生长在mwMEA板上的皮质神经元网络中自发活动的影响。每片含微电极12孔/孔，共768个通道。在被评估的30种化学物质中，23种已知能改变体内神经功能(“阳性”)，包括6种GABA能和3种谷氨酸能拮抗剂/激动剂、4种拟除虫菊酯类化合物、3种金属、2种胆碱酯酶抑制剂、2种烟碱型乙酰胆碱受体激动剂、丙戊酸、维拉帕米和氟西汀。7种预期对神经功能没有影响的化合物被测试为“阴性”(草甘膦、对乙酰氨基酚、水杨酸、百草枯、糖精、d-山梨醇和阿莫西林)。在收集了33分钟的基线活度后，记录了33分钟的化学效应(50微米或最高可溶性浓度)。其中20名阳性者改变了平均网络棘波率超过14%的阈值(与DMSO对照的平均值有两个标准偏差)。三种无效的阳性药分别是联苯菊酯、尼古丁和吡虫啉。没有一种负性化合物引起活性超过阈值的变化。基于这些结果，mwMEA检测具有很高的灵敏度(阳性化合物的识别率为87%)和特异性(阴性化合物的识别率为100%)。这些实验证明了mwMEA通过多种机制筛选化合物的神经毒性作用的能力。
Microelectrode array (MEA) approaches have been proposed as a tool for detecting functional changes in electrically excitable cells, including neurons, exposed to drugs, chemicals or particles. However, conventional single well-MEA systems lack the throughput necessary for screening large numbers of uncharacterized compounds. Recently, multi-well MEA (mwMEA) formats have become available to address the need for increased throughput. The current experiments examined the effects of a training set of 30 chemicals on spontaneous activity in networks of cortical neurons grown on mwMEA plates. Each plate contained 12 wells with 64 microelectrodes/well, for a total of 768 channels. Of the 30 chemicals evaluated, 23 were known to alter neuronal function in vivo (“positives”), including 6 GABAergic and 3 glutamatergic antagonists/agonists, 4 pyrethroids, 3 metals, 2 cholinesterase inhibitors, 2 nicotinic acetylcholine receptor agonists, valproic acid, verapamil, and fluoxetine. Seven compounds expected to have no effect on neuronal function were tested as “negatives” (glyphosate, acetaminophen, salicylic acid, paraquat, saccharin, d-sorbitol and amoxicillin). Following collection of 33 min of baseline activity, chemical effects (50 µM or highest soluble concentration) were recorded for 33 min. Twenty of the positives altered the mean network spike rate by more than the 14% threshold (two standard deviations from the mean for DMSO control). The three positives without effect were bifenthrin, nicotine and imidacloprid. None of the negative compounds caused a change in activity beyond the threshold. Based on these results, the mwMEA assay has both high sensitivity (87% identification of positive compounds) and specificity (100% identification of negative compounds). These experiments demonstrate the capacity of mwMEAs to screen compounds for neurotoxic effects mediated by a broad variety of mechanisms.
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影响因子：
1.8
作者：
Liu K;Southall N;Titus SA;Inglese J;Eskay RL;Shinn P;Austin CP;Heilig MA;Zheng W
通讯作者：
Zheng W
影响因子：
3.4
作者：
Keefer, EW;Norton, SJ;Gross, GW
通讯作者：
Gross, GW
影响因子：
3.4
作者：
Bal-Price, Anna K.;Sunol, Cristina;Costa, Lucio G.
通讯作者：
Costa, Lucio G.
影响因子：
3.1
作者：
Levkovitz, Y;Gil-Ad, I;Weizman, A
通讯作者：
Weizman, A
影响因子：
3.8
作者：
Breier, Joseph M.;Radio, Nicholas M.;Shafer, Timothy J.
通讯作者：
Shafer, Timothy J.