Int J Stem Cells.  2022 Aug;15(3):258-269. 10.15283/ijsc21217.

Establishment of Neurotoxicity Assessment Using Microelectrode Array (MEA) with hiPSC-Derived Neurons and Evaluation of New Psychoactive Substances (NPS)

• Kang Kr
• Kim CY
• Kim J
• Ryu B
• Lee SG
• Baek J
• Kim YJ
• Lee JM
• Lee Y
• Choi SO
• Woo DH
• Park IH
• Chung HM

• KMID: 2532400
• DOI: http://doi.org/10.15283/ijsc21217

Abstract

Background and Objectives
Currently, safety pharmacological tests for the central nervous system depend on animal behavioral analysis. However, due to the subjectivity of behavioral analysis and differences between species, there is a limit to appropriate nervous system toxicity assessment, therefore a new neurotoxicity assessment that can simulate the human central nervous system is required.
Methods and Results
In our study, we developed an in vitro neurotoxicity assessment focusing on neuronal function. To minimize the differences between species and fast screening, hiPSC-derived neurons and a microelectrode array (MEA) that could simultaneously measure the action potentials of the neuronal networks were used. After analyzing the molecular and electrophysiological characters of our neuronal network, we conducted a neurotoxicity assessment on neurotransmitters, neurotoxicants, illicit drugs, and new psychoactive substances (NPS). We found that most substances used in our experiments responded more sensitively to our MEA-based neurotoxicity assessment than to the conventional neurotoxicity assessment. Also, this is the first paper that evaluates various illicit drugs and NPS using MEA-based neurotoxicity assessment using hiPSC-derived neurons.
Conclusions
Our study expanded the scope of application of neurotoxicity assessment using hiPSC-derived neurons to NPS, and accumulated evaluation data of various toxic substances for hiPSC-derived neurons.

Keyword

Neurotoxicity assessment; Microelectrode array; iPSC-derived neuron application, Illicit drugs; New psychoactive substance

Figure

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  Fig. 1 Comparison of two neurotoxicity assays on neurotransmitters. (A) Concentration-response curves of neurotransmitter tested by MTT assay (solid line, *) or MEA (dotted line, #). MEA data were analyzed last 10 minutes of recording file described as above (N=10, M=5).

• 

  Fig. 2 Comparison of two neurotoxicity assays on neurotoxicants. (A) Concentration-response curves of neurotoxicant tested by MTT assay (solid line, *) or MEA (dotted line, #). MEA data were analyzed last 10 minutes of recording file described as above (N=10∼12, M=5).

• 

  Fig. 3 Comparison of two neurotoxicity assays on typical illicit drugs. (A) Concentration-response curves of classic illicit drug tested by MTT assay (solid line, *) or MEA (dotted line, #). MEA data were analyzed last 10 minutes of recording file described as above (N=10∼12, M=6).

• 

  Fig. 4 Comparison of two neurotoxicity assays on new psychoactive substances. (A) Concentration-response curves of new psychoactive substances tested by MTT assay (solid line, *) or MEA (dotted line, #). MEA data were analyzed last 10 minutes of recording file described as above (N=10∼12, M=6).

Reference

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