Burst and principal components analyses of MEA data for 16 chemicals describe at least three effects classes

Mack, Cina M.; Lin, Bryant J.; Turner, James D.; Johnstone, Andrew F.M.; Burgoon, Lyle D.; Shafer, Timothy J.

doi:10.1016/j.neuro.2013.11.008

Cited by 88 publications

(64 citation statements)

References 30 publications

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“…1). Spontaneous activity is correlated to neurite length and is sensitive to modulation by glutamatergic and GABAergic agonists and antagonists, modulators of voltage-gated sodium and calcium channels and other neurotoxic or neuroactive compounds (McConnell et al, 2012;Mack et al, 2014;Valdivia et al, 2014).…”

Section: Resultsmentioning

confidence: 99%

A multiplexed assay for determination of neurotoxicant effects on spontaneous network activity and viability from microelectrode arrays

et al. 2015

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Section: Resultsmentioning

confidence: 99%

A multiplexed assay for determination of neurotoxicant effects on spontaneous network activity and viability from microelectrode arrays

et al. 2015

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“…3), and bursting was virtually absent in iCell neurons and HIP neurons. Bursting parameters may help identify different groups of chemicals (Alloisio et al, 2015;Mack et al, 2014), although it has previously been shown that adding bursting parameters does not result in an increased sensitivity to detect neurotoxic chemicals in MEA-based screening approaches (Defranchi et al, 2011;Shafer et al, 2008;Dingemans et al, submitted) and the MSR alone provides sufficient information for a first screening (McConnell et al, 2012). Additionally, the increasing throughput of mwMEA systems, currently up to 96-wells with only 8 electrodes per well, will continue to hamper detailed analysis of network synchrony.…”

Section: Referencesmentioning

confidence: 99%

Is the time right for in vitro neurotoxicity testing using human iPSC-derived neurons?

Tukker

Groot

Wijnolts

et al. 2016

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“…Consequently, ToCP and TmCP may have different modes of action. So far, increases in MSR have been largely limited to glutamatergic agonists and GABAergic antagonists (McConnell et al, 2012;Mack et al, 2014). Since prolonged exposure to ToCP was recently reported to decrease glutamatergic signaling (Hausherr et al, 2014), it is tempting to speculate that the neurotoxicity of ToCP also involves modulation of glutamatergic receptors.…”

Section: Discussionmentioning

confidence: 99%

In vitro neurotoxic hazard characterization of different tricresyl phosphate (TCP) isomers and mixtures

et al. 2017

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A B S T R A C TExposure to tricresyl phosphates (TCPs), via for example contaminated cabin air, has been associated with health effects including the so-called aerotoxic syndrome. While TCP neurotoxicity is mainly attributed to ortho-isomers like tri-ortho-cresyl phosphate (ToCP), recent exposure and risk assessments indicate that ToCP levels in cabin air are very low. However, the neurotoxic potential of non-ortho TCP isomers and TCP mixtures is largely unknown. We therefore measured effects of exposure (up to 48 h) to different TCP isomers, mixtures and the metabolite of ToCP (CBDP: cresyl saligenin phosphate) on cell viability and mitochondrial activity, spontaneous neuronal electrical activity, and neurite outgrowth in primary rat cortical neurons.The results demonstrate that exposure to TCPs (24-48 h, up to 10 mM) increases mitochondrial activity, without affecting cell viability. Effects of acute TCP exposure (30 min) on neuronal electrical activity are limited. However, electrical activity is markedly decreased for the majority of TCPs (10 mM) following 48 h exposure. Additional preliminary data indicate that exposure to TCPs (48 h, 10 mM) did not affect the number of neurites per cell or average neurite length, except for TmCP and the analytical TCP mixture (Sigma) that induced a reduction of average neurite length.The combined neurotoxicity data demonstrate that the different TCPs, including ToCP, are roughly equipotent and a clear structure-activity relation is not apparent for the studied endpoints. The noobserved-effect-concentrations (1 mM) are well above current exposure levels indicating limited neurotoxic health risk, although exposures may have been higher in the past. Moreover, prolonged and/or repeated exposure to TCPs may exacerbate the observed neurotoxic effects, which argues for additional research.

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Burst and principal components analyses of MEA data for 16 chemicals describe at least three effects classes

Cited by 88 publications

References 30 publications

A multiplexed assay for determination of neurotoxicant effects on spontaneous network activity and viability from microelectrode arrays

A multiplexed assay for determination of neurotoxicant effects on spontaneous network activity and viability from microelectrode arrays

Is the time right for in vitro neurotoxicity testing using human iPSC-derived neurons?

In vitro neurotoxic hazard characterization of different tricresyl phosphate (TCP) isomers and mixtures

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