Evaluation of Chemical Effects on Network Formation in Cortical Neurons Grown on Microelectrode Arrays.
Evaluation of Chemical Effects on Network Formation in Cortical Neurons Grown on Microelectrode Arrays.
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微电极阵列上生长的皮质神经元网络形成的化学效应评估。
DOI：
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发表时间：
2019
影响因子：
3.8
通讯作者：
K. P. Friedman
中科院分区：
文献类型：
--
作者：
T. Shafer;Jasmine P. Brown;Brittany S Lynch;Sylmarie Dávila;Kathleen A. Wallace;K. P. Friedman
人类可能接触的数千种化学物质尚未进行潜在发育神经毒性（DNT）评估，这推动了开发一系列体外筛选DNT危害方法的努力。在这里，136个独特的化学品进行了评估，潜在的DNT危害使用网络形成试验（NFA）在微电极阵列上生长的皮质细胞。在DIV 5、7、9和12评价了从接种后2 h至体外（DIV）12天的化学暴露对网络形成的影响，并在DIV 12评估了细胞活力。只有82种化学物质改变了至少1个网络发育参数。含量测定结果具有重现性;作为生物学重复检测的10种化学品产生了100%一致的定性结果，效价值一致。确定了58种化学品的毒理学临界点，这些临界点与所有参数的最低50%效应浓度（EC 50）相似或低于该浓度。当将NFA的EC 50和临界点值与ToxCast测定中观察到的效价范围进行比较时，NFA EC 50值小于一部分化学品的ToxCast测定效价的下四分位数，其中许多化学品在体内具有急性神经毒性。对于13种具有体内DNT数据的化学品，基于NFA结果的估计给药剂量等效剂量与体内给药剂量相似或低于体内给药剂量。总的来说，这些结果表明，NFA是敏感的化学品作用于神经系统功能，将是一个有价值的贡献，在体外DNT筛选电池。
Thousands of chemicals to which humans are potentially exposed have not been evaluated for potential developmental neurotoxicity (DNT), driving efforts to develop a battery of in vitro screening approaches for DNT hazard. Here, 136 unique chemicals were evaluated for potential DNT hazard using a network formation assay (NFA) in cortical cells grown on microelectrode arrays. The effects of chemical exposure from 2 h postplating through 12 days in vitro (DIV) on network formation were evaluated at DIV 5, 7, 9, and 12, with cell viability assessed at DIV 12. Only 82 chemicals altered at least 1 network development parameter. Assay results were reproducible; 10 chemicals tested as biological replicates yielded qualitative results that were 100% concordant, with consistent potency values. Toxicological tipping points were determined for 58 chemicals and were similar to or lower than the lowest 50% effect concentrations (EC50) for all parameters. When EC50 and tipping point values from the NFA were compared to the range of potencies observed in ToxCast assays, the NFA EC50 values were less than the lower quartile for ToxCast assay potencies for a subset of chemicals, many of which are acutely neurotoxic in vivo. For 13 chemicals with available in vivo DNT data, estimated administered equivalent doses based on NFA results were similar to or lower than administered doses in vivo. Collectively, these results indicate that the NFA is sensitive to chemicals acting on nervous system function and will be a valuable contribution to an in vitro DNT screening battery.
影响因子：
6.1
作者：
Krug, Anne K.;Kolde, Raivo;Gaspar, John A.;Rempel, Eugen;Balmer, Nina V.;Meganathan, Kesavan;Vojnits, Kinga;Baquie, Mathurin;Waldmann, Tanja;Ensenat-Waser, Roberto;Jagtap, Smita;Evans, Richard M.;Julien, Stephanie;Peterson, Hedi;Zagoura, Dimitra;Kadereit, Suzanne;Gerhard, Daniel;Sotiriadou, Isaia;Heke, Michael;Natarajan, Karthick;Henry, Margit;Winkler, Johannes;Marchan, Rosemarie;Stoppini, Luc;Bosgra, Sieto;Westerhout, Joost;Verwei, Miriam;Vilo, Jaak;Kortenkamp, Andreas;Hescheler, Jurgen;Hothorn, Ludwig;Bremer, Susanne;van Thriel, Christoph;Krause, Karl-Heinz;Hengstler, Jan G.;Rahnenfuehrer, Jorg;Leist, Marcel;Sachinidis, Agapios
通讯作者：
Sachinidis, Agapios
影响因子：
3.4
作者：
McConnell, Emma R.;McClain, Maxine A.;Ross, James;LeFew, William R.;Shafer, Timothy J.
通讯作者：
Shafer, Timothy J.
影响因子：
3.4
作者：
Wilson, W. Wyatt;Shapiro, Lauren P.;Bradner, Joshua M.;Caudle, W. Michael
通讯作者：
Caudle, W. Michael