Neurotoxicity screening of (illicit) drugs using novel methods for analysis of microelectrode array (MEA) recordings

Hondebrink, Laura; Verboven, Anouk H.A.; Drega, W S; Schmeink, S.; Groot, Martje W G D M de; Kleef, Regina G.D.M. van; Wijnolts, Fiona M.J.; Groot, Aart de; Meulenbelt, Jan; Westerink, Remco H.S.

doi:10.1016/j.neuro.2016.04.020

Cited by 62 publications

(82 citation statements)

References 35 publications

(46 reference statements)

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“…While the costs of human iPSC-derived neurons are still high compared to primary cultures, the availability of human iPSC-derived neurons from particular brain areas and/or patients suffering from a particular neurological disorder opens the iCell neurons for an explorative functional screening, using different physiological, pharmacological and toxicological stimuli. This initial assessment demonstrated that MEA data obtained with iCell neurons are largely in line with previous data from primary cultures (McConnell et al, 2012;Hogberg et al, 2011;Dingemans et al, submitted;Hondebrink et al, 2016) and human embryonic stem cell-derived neurons (Ylä-Outinen et al, 2010). Moreover, iCell neurons challenged with endosulfan or amphetamine (Fig.…”

Section: Discussionsupporting

confidence: 85%

“…Finally, when iCell neurons were challenged with the widely used drug of abuse amphetamine, the MSR showed a concentration-dependent decrease (Fig. 4B) as also observed for primary rat cortical neurons (Hondebrink et al, 2016).…”

Section: Modulation Of Electrical Activity Of Icell Neuronssupporting

confidence: 69%

“…Moreover, iCell neurons challenged with endosulfan or amphetamine (Fig. 4), showed changes in neuronal activity comparable with primary rat cortical neurons (Dingemans et al, submitted;Hondebrink et al, 2016), indicating not only the presence and functionality of different neurotransmitter receptors, but also the potential for chemical neurotoxicity screening.…”

Section: Discussionmentioning

confidence: 72%

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

Tukker

Groot

Wijnolts

et al. 2016

ALTEX

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Section: Discussionsupporting

confidence: 85%

Section: Modulation Of Electrical Activity Of Icell Neuronssupporting

confidence: 69%

Section: Discussionmentioning

confidence: 72%

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

Tukker

Groot

Wijnolts

et al. 2016

ALTEX

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“…We have previously shown that (over)excitation of the network often manifests as an inhibition of neuronal activity in MEA recordings. For example, exposure to high concentrations of glutamate or to excitatory chemicals, such as pyrethroid-and organophosphorus insecticides, decreases neuronal activity (Dingemans et al, 2016;Hondebrink et al, 2016;Meyer et al, 2008;Tukker et al, 2016;Vassallo et al, 2016), despite the clear excitatory effects of these substances on individual cells. Although MEA recordings of neuronal activity are very suitable to screen for drug effects, they are less suitable to pinpoint the exact underlying (individual) mechanisms.…”

Section: Discussionmentioning

confidence: 99%

“…Rat primary cortical cells were isolated from the neonatal cortex from post-natal day (PND) 1 Wistar rat pups as described previously Hondebrink et al, 2016). Briefly, rat pups were decapitated and cortices were rapidly dissected on ice.…”

Section: Rat Primary Cortical Cellsmentioning

confidence: 99%

Neuropharmacological characterization of the new psychoactive substance methoxetamine

et al. 2017

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a b s t r a c tThe use of new psychoactive substances (NPS) is steadily increasing. One commonly used NPS is methoxetamine (MXE), a ketamine analogue. Several adverse effects have been reported following MXE exposure, while only limited data are available on its neuropharmacological modes of action.We investigated the effects of MXE and ketamine on several endpoints using multiple in vitro models. These included rat primary cortical cells, human SH-SY5Y cells, human induced pluripotent stem cell (hiPSC)-derived iCell ® Neurons, DopaNeurons and astrocyte co-cultures, and human embryonic kidney (HEK293) cells. We investigated effects on several neurotransmitter receptors using single cell intracellular calcium [Ca 2þ ] i imaging, effects on neuronal activity using micro-electrode array (MEA) recordings and effects on human monoamine transporters using a fluorescence-based plate reader assay.In rat primary cortical cells, 10 mM MXE increased the glutamate-evoked increase in [Ca 2þ ] i , whereas 10 mM ketamine was without effect. MXE and ketamine did not affect voltage-gated calcium channels (VGCCs), but inhibited spontaneous neuronal activity (IC 50 0.5 mM and 1.2 mM respectively). In human SH-SY5Y cells, 10 mM MXE slightly inhibited the K Our combined in vitro data provide an urgently needed first insight into the multiple modes of action of MXE. The use of different models and different (neuronal) endpoints can be complementary in pharmacological profiling. Rapid in vitro screening methods as those presented here, could be of utmost importance for gaining a first mechanistic insight to aid the risk assessment of emerging NPS.

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Using Human‐Induced Pluripotent Stem Cell Derived Neurons on Microelectrode Arrays to Model Neurological Disease: A Review

Lv,

He,

Luo

et al. 2023

Advanced Science

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In situ physiological signals of in vitro neural disease models are essential for studying pathogenesis and drug screening. Currently, an increasing number of in vitro neural disease models are established using human‐induced pluripotent stem cell (hiPSC) derived neurons (hiPSC‐DNs) to overcome interspecific gene expression differences. Microelectrode arrays (MEAs) can be readily interfaced with two‐dimensional (2D), and more recently, three‐dimensional (3D) neural stem cell‐derived in vitro models of the human brain to monitor their physiological activity in real time. Therefore, MEAs are emerging and useful tools to model neurological disorders and disease in vitro using human iPSCs. This is enabling a real‐time window into neuronal signaling at the network scale from patient derived. This paper provides a comprehensive review of MEA's role in analyzing neural disease models established by hiPSC‐DNs. It covers the significance of MEA fabrication, surface structure and modification schemes for hiPSC‐DNs culturing and signal detection. Additionally, this review discusses advances in the development and use of MEA technology to study in vitro neural disease models, including epilepsy, autism spectrum developmental disorder (ASD), and others established using hiPSC‐DNs. The paper also highlights the application of MEAs combined with hiPSC‐DNs in detecting in vitro neurotoxic substances. Finally, the future development and outlook of multifunctional and integrated devices for in vitro medical diagnostics and treatment are discussed.

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Neurotoxicity screening of (illicit) drugs using novel methods for analysis of microelectrode array (MEA) recordings

Cited by 62 publications

References 35 publications

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

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

Neuropharmacological characterization of the new psychoactive substance methoxetamine

Using Human‐Induced Pluripotent Stem Cell Derived Neurons on Microelectrode Arrays to Model Neurological Disease: A Review

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