Abstract：
: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 3072 wells per week, we screened a well-characterized library of 1280 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.
journal_name
Toxicol Appl Pharmacoljournal_title
Toxicology and applied pharmacologyauthors
Vliet SM,Ho TC,Volz DCdoi
10.1016/j.taap.2017.06.011subject
Has Abstractpub_date
2017-08-15 00:00:00pages
241-248eissn
0041-008Xissn
1096-0333pii
S0041-008X(17)30267-3journal_volume
329pub_type
杂志文章abstract：:We expressed rat Na(v)1.6 sodium channels in combination with the rat beta(1) and beta(2) auxiliary subunits in Xenopus laevis oocytes and evaluated the effects of the pyrethroid insecticides S-bioallethrin, deltamethrin, and tefluthrin on expressed sodium currents using the two-electrode voltage clamp technique. S-Bi...
journal_title：Toxicology and applied pharmacology
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journal_title：Toxicology and applied pharmacology
pub_type： 杂志文章,评审
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doi：10.1006/taap.2001.9189
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journal_title：Toxicology and applied pharmacology
pub_type： 杂志文章
doi：10.1006/taap.1994.1175
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journal_title：Toxicology and applied pharmacology
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journal_title：Toxicology and applied pharmacology
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journal_title：Toxicology and applied pharmacology
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journal_title：Toxicology and applied pharmacology
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journal_title：Toxicology and applied pharmacology
pub_type： 杂志文章
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journal_title：Toxicology and applied pharmacology
pub_type： 杂志文章
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journal_title：Toxicology and applied pharmacology
pub_type： 杂志文章
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journal_title：Toxicology and applied pharmacology
pub_type： 杂志文章
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journal_title：Toxicology and applied pharmacology
pub_type： 杂志文章
doi：10.1016/0041-008x(84)90143-1
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journal_title：Toxicology and applied pharmacology
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journal_title：Toxicology and applied pharmacology
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journal_title：Toxicology and applied pharmacology
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journal_title：Toxicology and applied pharmacology
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journal_title：Toxicology and applied pharmacology
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journal_title：Toxicology and applied pharmacology
pub_type： 杂志文章
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abstract：:Polychlorinated biphenyls (PCBs) are a group of persistent and widely distributed environmental pollutants that have various deleterious effects, e.g., neurotoxicity, endocrine disruption and reproductive abnormalities. In order to verify the hypothesis that the PI3K/Akt and MAPK pathways play important roles in hepat...
journal_title：Toxicology and applied pharmacology
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journal_title：Toxicology and applied pharmacology
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doi：10.1016/j.taap.2008.07.022
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journal_title：Toxicology and applied pharmacology
pub_type： 杂志文章,评审
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journal_title：Toxicology and applied pharmacology
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journal_title：Toxicology and applied pharmacology
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journal_title：Toxicology and applied pharmacology
pub_type： 杂志文章
doi：10.1016/0041-008x(92)90319-n
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abstract：:Two hours after a four-hour exposure to hexamethylene diisocyanate trimer (HDIt) aerosol between 2.5 and 39 mg/m3, mice were injected iv with 51Cr-EDTA (chromium ethylenediaminetetraacetate). Ten minutes later the lung was lavaged. A larger amount of 51Cr-EDTA was detected in the lung lavage of HDIt mice than of contr...
journal_title：Toxicology and applied pharmacology
pub_type： 杂志文章
doi：10.1016/0041-008x(83)90269-7
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abstract：:Liver fibrosis results from chronic tissue damage and excessive regeneration with accumulation of extracellular matrix proteins; it is a precursor of liver cirrhosis and hepatocellular carcinoma. Liver fibrosis treatments are primarily directed at inflammation, with few options to combat fibrogenesis. Pirfenidone is a...
journal_title：Toxicology and applied pharmacology
pub_type： 杂志文章
doi：10.1016/j.taap.2017.11.024
更新日期：2018-01-15 00:00:00
abstract：:The teleost swim bladder is assumed a homolog of the tetrapod lung. Both swim bladder and lung are developmental targets of persistent aryl hydrocarbon receptor (AHR(2)) agonists; in zebrafish (Danio rerio) the swim bladder fails to inflate with exposure to 3,3',4,4',5-pentachlorobiphenyl (PCB126). The mechanism for t...
journal_title：Toxicology and applied pharmacology
pub_type： 杂志文章
doi：10.1016/j.taap.2012.09.023
更新日期：2012-12-01 00:00:00
