Zebrafish provide a sensitive model of persisting neurobehavioral effects of developmental chlorpyrifos exposure: comparison with nicotine and pilocarpine effects and relationship to dopamine deficits.
Zebrafish provide a sensitive model of persisting neurobehavioral effects of developmental chlorpyrifos exposure: comparison with nicotine and pilocarpine effects and relationship to dopamine deficits.
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DOI：
10.1016/j.ntt.2009.02.005
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发表时间：
2010-01
影响因子：
2.9
通讯作者：
Levin, Edward D.
中科院分区：
文献类型：
--
作者：
Eddins, Donnie;Cerutti, Daniel;Williams, Paul;Linney, Elwood;Levin, Edward D.
毒死蜱（CPF）是一种有机磷农药，当暴露于大鼠模型的早期发育过程中时，会导致持续的行为障碍。在早期的工作中，斑马鱼被用作补充模型来研究在早期发育过程中诱导的CPF诱导的神经毒性的机制。我们发现，发育（受精后的前五天）毒死蜱暴露显着损害斑马鱼的学习。然而，这种测试是时间和劳动密集型的。在目前的研究中，我们测试了这一假设，即持续影响的发展毒死蜱可以检测到一个简短的自动评估惊吓反应，这种行为指数可以用来帮助确定持续CPF影响的神经行为机制。成年斑马鱼的游泳活动在突然敲击测试竞技场后通过计算机视频跟踪设备进行评估。进行10次连续试验（1/min）以确定惊吓反应及其习惯化。此外，在初始试验组结束后8、32和128分钟进行习惯化恢复试验。与对照组相比，暴露于CPF的鱼在10次试验期间显示出显著（p<0.025）更大的总体惊吓反应（组大小：对照组N=40，CPF N=24）。在最初的恢复期（8分钟），暴露于CPF的鱼显示出显着（p<0.01）更大的惊吓反应相比，控制。为了阐明烟碱和毒蕈碱乙酰胆碱受体对发育性CPP介导的作用的贡献，测定了受精后前五天发育性尼古丁和毛果芸香碱暴露的影响。发育期尼古丁和毛果芸香碱暴露显著增加惊吓反应，尽管尼古丁（组大小：对照N=32，15 mM N=12，25 mM N=20）比毛果芸香碱（组大小：对照N=20，100 μM N=16，1000 μM N=12）更有效。在成年期，CPF对发育暴露增加惊吓反应的作用都不如CPF。最后，发育CPF暴露降低了多巴胺和5-羟色胺水平，并增加了发育中的斑马鱼幼虫（N=4批50个胚胎/治疗）的递质周转。只有多巴胺浓度的下降持续到成年期（组大小：对照组N=14，CPF N=13）。这项研究表明，一个快速的自动测试惊吓可以检测持续的神经行为障碍所造成的发展暴露于CPF。这可能有助于筛选持续的神经行为缺陷的各种毒物。
Chlorpyrifos (CPF) an organophosphate pesticide causes persisting behavioral dysfunction in rat models when exposure is during early development. In earlier work zebrafish were used as a complementary model to study mechanisms of CPF-induced neurotoxicity induced during early development. We found that developmental (first five days after fertilization) chlorpyrifos exposure significantly impaired learning in zebrafish. However, this testing was time and labor intensive. In the current study we tested the hypothesis that persisting effects of developmental chlorpyrifos could be detected with a brief automated assessment of startle response and that this behavioral index could be used to help determine the neurobehavioral mechanisms for persisting CPF effects. The swimming activity of adult zebrafish was assessed by a computerized video-tracking device after a sudden tap to the test arena. Ten consecutive trials (1/min) were run to determine startle response and its habituation. Additionally, habituation recovery trials were run at 8, 32 and 128 min after the end of the initial trial set. CPF-exposed fish showed a significantly (p<0.025) greater overall startle response during the 10-trial session compared to controls (group sizes: Control N=40, CPF N=24). During the initial recovery period (8 min) CPF-exposed fish showed a significantly (p<0.01) greater startle response compared to controls. To elucidate the contributions of nicotinic and muscarinic acetylcholine receptors to developmental CPF-mediated effects, the effects of developmental nicotine and pilocarpine exposure throughout the first five days after fertilization were determined. Developmental nicotine and pilocarpine exposure significantly increased startle response, though nicotine (group sizes: Control N=32, 15 mM N=12, 25 mM N=20) was much more potent than pilocarpine (group sizes: Control N=20, 100 μM N=16, 1000 μM N=12). Neither was as potent as CPF for developmental exposure increasing startle response in adulthood. Lastly, developmental CPF exposure decreased dopamine and serotonin levels and increased transmitter turnover in developing zebrafish larvae (N=4 batches of 50 embryos/treatment). Only the decline in dopamine concentrations persisted into adulthood (group sizes: Control N=14, CPF N=13). This study shows that a quick automated test of startle can detect persisting neurobehavioral impairments caused by developmental exposure to CPF. This may be helpful in screening for persisting neurobehavioral defects from a variety of toxicants.
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影响因子：
1.3
作者：
Colwill, RM;Raymond, MP;Escudero, H
通讯作者：
Escudero, H
影响因子：
3.4
作者：
Karen, DJ;Li, W;Bloomquist, JR
通讯作者：
Bloomquist, JR
影响因子：
5.3
作者：
Gerfen, CR;Miyachi, S;Brown, P
通讯作者：
Brown, P
影响因子：
5.3
作者：
Burgess, Harold A.;Granato, Michael
通讯作者：
Granato, Michael
DOI：
10.1016/s0165-3806(01)00215-2
发表时间：
2001-09-23
期刊：
DEVELOPMENTAL BRAIN RESEARCH
影响因子：
--
作者：
Levin, ED;Addy, N;Slotkin, TA
通讯作者：
Slotkin, TA