Development of a novel method for neural activity assessment using microelectrode array technology
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Neurological disorders are related to exposure to various environmental toxicants. However, the toxicity evaluation of environmental chemicals through animal testing has challenges due to time delay and ethical problem. There are needs for advanced neurotoxicity assessments. The development of alternative toxicity testing methods is crucial for improving the time efficiency and accuracy of chemical safety evaluations while addressing ethical concerns regarding animal use. In this study, we introduce an innovative in vitro neurotoxicity assessment platform that integrates microelectrode array (MEA) technology to evaluate neuronal activity and network dynamics. Unlike conventional methods, MEA analysis provides real-time, high-resolution insights into functional changes in neuronal networks, enabling a deeper understanding of neurotoxic effects. Primary cortical neurons derived from fetal rats were cultured on MEA plates. Neuronal activity was monitored across six parameters: the number of active electrodes, mean firing rate, burst rate, spike-in-burst ratio, network burst, and synchrony index. This robust analytical framework facilitated the detection of subtle changes in neuronal function in neurotoxicity assessments. By focusing on functional neurophysiology, this method paves the way for more ethical, efficient, and precise toxicity testing. These findings suggested developing standardized alternative neuronal toxicity testing protocols. This platform not only enhances our ability to evaluate neurotoxic effects but also represents a significant step toward reducing animal use in toxicity research while improving safety evaluations for chemicals and pharmaceuticals.
Abstract
Neurological disorders are related to exposure to various environmental toxicants. However, the toxicity evaluation of environmental chemicals through animal testing has challenges due to time delay and ethical problem. There are needs for advanced neurotoxicity assessments. The development of alternative toxicity testing methods is crucial for improving the time efficiency and accuracy of chemical safety evaluations while addressing ethical concerns regarding animal use. In this study, we introduce an innovative in vitro neurotoxicity assessment platform that integrates microelectrode array (MEA) technology to evaluate neuronal activity and network dynamics. Unlike conventional methods, MEA analysis provides real-time, high-resolution insights into functional changes in neuronal networks, enabling a deeper understanding of neurotoxic effects. Primary cortical neurons derived from fetal rats were cultured on MEA plates. Neuronal activity was monitored across six parameters: the number of active electrodes, mean firing rate, burst rate, spike-in-burst ratio, network burst, and synchrony index. This robust analytical framework facilitated the detection of subtle changes in neuronal function in neurotoxicity assessments. By focusing on functional neurophysiology, this method paves the way for more ethical, efficient, and precise toxicity testing. These findings suggested developing standardized alternative neuronal toxicity testing protocols. This platform not only enhances our ability to evaluate neurotoxic effects but also represents a significant step toward reducing animal use in toxicity research while improving safety evaluations for chemicals and pharmaceuticals.
참고문헌 (29)
- Aleya, L., "Environmental pollutants and the risk of neurological disorders", Environmental Science and Pollution Research, 27(36), pp.44657~44658 (2020)
- Alloisio, S., "Multiparametric characterisation of neuronal network activity for in vitro agrochemical neurotoxicity assessment", Neurotoxicology, 48, pp.152~165 (2015)
- Amin, H., "Long-term multielectrode array recordings of neuronal networks for toxicity testing", Toxicology In Vitro, 62, pp.104644~ (2020)
- Anitha, M., "Characterization of fetal and postnatal enteric neuronal cell lines with improvement in intestinal neural function", Gastroenterology, 134(5), pp.1424~1435 (2008)
- Bennett, D., "Project TENDR: targeting environmental neurodevelopmental risks the TENDR consensus statement", Environmental health perspectives, 124(7), pp.A118~A122 (2016)
- Chiappalone, M., "Network plasticity in cortical assemblies", The European Journal of Neuroscience, 28(1), pp.221~230 (2007)
- Coecke, S., "Workgroup report : incorporating in vitro alternative methods for developmental neurotoxicity into international hazard and risk assessment strategies", Environmental health perspectives, 115(6), pp.924~931 (2007)
- Doke, S. K., "Alternatives to animal testing : A review", Saudi Pharmaceutical Journal, 23(3), pp.223~229 (2015)
- Druwe, I., "Sensitivity of neuroprogenitor cells to chemical-induced apoptosis using a multiplexed assay suitable for high-throughput screening", Toxicology, 333, pp.14~24 (2015)
- Frank, C. L., "From the cover : developmental neurotoxicants disrupt activity in cortical networks on microelectrode arrays : results of screening 86 compounds during neural network formation", Toxicological Sciences, 160(1), pp.121~135 (2017)
- Grabrucker, A., "Synaptogenesis of hippocampal neurons in primary cell culture", Cell and Tissue Research, 338, pp.333~341 (2009)
- Grandjean, P., "Developmental neurotoxicity of industrial chemicals", The Lancet, 368(9553), pp.2167~2178 (2006)
- Harrill, J. A., "Quantitative assessment of neurite outgrowth in human embryonic stem cell-derived hN2™ cells using automated high-content image analysis", Neurotoxicology, 31(3), pp.277~290 (2010)
- Heikkilä, T. J., "Human embryonic stem cell-derived neuronal cells form spontaneously active neuronal networks in vitro", Experimental Neurology, 218(1), pp.109~116 (2009)
- Huh, D., "Reconstituting organ-level lung functions on a chip", Science, 328(5986), pp.1662~1668 (2010)
- Jakaria, M., "Neurotoxic agent-induced injury in neurodegenerative disease model : Focus on involvement of glutamate receptors", Frontiers in molecular neuroscience, 11, pp.307~ (2018)
- Johnstone, A. F., "Microelectrode arrays : a physiologically based neurotoxicity testing platform for the 21st century", Neurotoxicology, 31(4), pp.331~350 (2010)
- Kato-Negishi, M., "Developmental changes of GABAergic synapses formed between primary cultured cortical neurons", Developmental brain research, 152(2), pp.99~108 (2004)
- Koch, K., "Scientific validation of human neurosphere assays for developmental neurotoxicity evaluation", Frontiers in Toxicology, 4, pp.816370~ (2022)
- Landrigan, P. J., "Early environmental origins of neurodegenerative disease in later life", Environmental health perspectives, 113(9), pp.1230~1233 (2005)
- Legradi, J. B., "An ecotoxicological view on neurotoxicity assessment", Environmental Sciences Europe, 30, pp.1~34 (2018)
- Liu, G., "Local structural balance and functional interaction of excitatory and inhibitory synapses in hippocampal dendrites", Nature Neuroscience, 7(4), pp.373~379 (2004)
- Makris, S. L., "A retrospective performance assessment of the developmental neurotoxicity study in support of OECD test guideline 426", Environmental health perspectives, 117(1), pp.17~25 (2009)
- Novellino, A., "Development of micro-electrode array-based tests for neurotoxicity : Assessment of inter-laboratory reproducibility with neuroactive chemicals", Frontiers in Neuroengineering, 4, pp.4~ (2011)
- Nyffeler, J., "Combination of multiple neural crest migration assays to identify environmental toxicants from a proof-of-concept chemical library", Archives of toxicology, 91, pp.3613~3632 (2017)
- Spencer, C., "Electrophysiological recordings from neuronal networks using multielectrode arrays", Current Protocols in Pharmacology, 54(1), pp.12~25 (2011)
- Tatti, R., "Neurophysiology and regulation of the balance between excitation and inhibition in neocortical circuits", Biological Psychiatry, 81(10), pp.821~831 (2017)
- Wallace, K., "A multiplexed assay for determination of neurotoxicant effects on spontaneous network activity and viability from microelectrode arrays", Neurotoxicology, 49, pp.79~85 (2015)
- Zeliger, H. I., "Exposure to lipophilic chemicals as a cause of neurological impairments, neurodevelopmental disorders and neurodegenerative diseases", Interdisciplinary Toxicology, 6(3), pp.103~110 (2013)
