Behavioral screening of the LOPAC(1280) library in zebrafish embryos.
Behavioral screening of the LOPAC(1280) library in zebrafish embryos.
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DOI：
10.1016/j.taap.2017.06.011
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发表时间：
2017-08-15
影响因子：
3.8
通讯作者：
Volz DC
中科院分区：
文献类型：
--
作者：
Vliet SM;Ho TC;Volz DC
自发活动代表了斑马鱼胚胎内运动活动的早期原始形式，为识别神经活性化合物提供了潜在的读出。然而，尽管在世界各地的化学筛选中用作终点，但依赖于自发活动的测定的预测能力和局限性仍然不清楚。使用改进的高含量筛选测定，将通量从每周384个孔增加到3，072个威尔斯，我们筛选了1，280种具有生物活性的化合物（LOPAC 1280）的充分表征的文库-其中612种靶向神经传递-以鉴定使用自发活性作为读数检测到哪些靶标。该筛选的结果显示：（1）8%的LOPAC 1280文库具有生物活性;（2）自发活性受跨越广泛靶点的化合物的影响;（3）仅4%靶向神经传递的化合物影响自发活性;和（4）对于100%检测到的命中，包括对相同靶表现出相反作用机制的命中，观察到活性减退。因此，虽然该试验能够快速鉴定有效的神经活性化学物质，但这些数据表明，自发活动可能缺乏区分干扰神经传递的化合物的作用模式的能力，这一问题可能是由于水性暴露后的全身摄取、持续的对照变异和/或干扰非神经传递相关机制所致。
Spontaneous activity represents an early, primitive form of motor activity within zebrafish embryos, providing a potential readout for identification of neuroactive compounds. However, despite use as an endpoint in chemical screens around the world, the predictive power and limitations of assays relying on spontaneous activity remain unclear. Using an improved high-content screening assay that increased throughput from 384 to 3,072 wells per week, we screened a well-characterized library of 1,280 pharmacologically active compounds (LOPAC1280) – 612 of which target neurotransmission – to identify which targets are detected using spontaneous activity as a readout. Results from this screen revealed that (1) 8% of the LOPAC1280 library was biologically active; (2) spontaneous activity was affected by compounds spanning a broad array of targets; (3) only 4% of compounds targeting neurotransmission impacted spontaneous activity; and (4) hypoactivity was observed for 100% of hits detected, including those that exhibit opposing mechanisms of action for the same target. Therefore, while this assay was able to rapidly identify potent neuroactive chemicals, these data suggest that spontaneous activity may lack the ability to discriminate modes of action for compounds interfering with neurotransmission, an issue that may be due to systemic uptake following waterborne exposure, persistent control variation, and/or interference with non-neurotransmission-related mechanisms.
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影响因子：
2.7
作者：
Egan, Rupert J.;Bergner, Carisa L.;Hart, Peter C.;Cachat, Jonathan M.;Canavello, Peter R.;Elegante, Marco F.;Elkhayat, Salem I.;Bartels, Brett K.;Tien, Anna K.;Tien, David H.;Mohnot, Sopan;Beeson, Esther;Glasgow, Eric;Amri, Hakima;Zukowska, Zofia;Kalueff, Allan V.
通讯作者：
Kalueff, Allan V.
影响因子：
3.3
作者：
Gustafson, A. -L.;Stedman, D. B.;Augustine-Rauch, K. A.
通讯作者：
Augustine-Rauch, K. A.
DOI：
10.1523/jneurosci.3689-12.2013
发表时间：
2013-02-27
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Kokel D;Dunn TW;Ahrens MB;Alshut R;Cheung CY;Saint-Amant L;Bruni G;Mateus R;van Ham TJ;Shiraki T;Fukada Y;Kojima D;Yeh JR;Mikut R;von Lintig J;Engert F;Peterson RT
通讯作者：
Peterson RT
影响因子：
25
作者：
Behra, M;Cousin, X;Strähle, U
通讯作者：
Strähle, U
影响因子：
3.5
作者：
Knogler, Laura D.;Drapeau, Pierre
通讯作者：
Drapeau, Pierre