Real-Time Monitoring of Levetiracetam Effect on the Electrophysiology of an Heterogenous Human iPSC-Derived Neuronal Cell Culture Using Microelectrode Array Technology
Abstract
:1. Introduction
2. Materials and Methods
2.1. Cell Culture
2.2. MEA Plates Coating, and Seeding of Ncyte CNS Cells
2.3. LEV Treatment, MEA Recordings, and Data Processing
2.4. Analyzed Variables
2.5. Statistical Analysis
3. Results
3.1. Spiking
3.2. Single-Electrode Bursting
3.3. Network Bursting
3.4. Raster Plots: A Qualitative Description of Complex Neural Activity
3.5. Spike Amplitude
4. Discussion
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Data Availability Statement
Conflicts of Interest
References
- Marcotulli, D.; Fattorini, G.; Bragina, L.; Perugini, J.; Conti, F. Levetiracetam Affects Differentially Presynaptic Proteins in Rat Cerebral Cortex. Front. Cell. Neurosci. 2017, 11, 389. [Google Scholar] [CrossRef] [PubMed]
- Kumar, A.; Maini, K.; Kadian, R. Levetiracetam. In StatPearls; StatPearls Publishing: Treasure Island, FL, USA, 2021. [Google Scholar]
- Deshpande, L.S.; DeLorenzo, R.J. Mechanisms of Levetiracetam in the Control of Status Epilepticus and Epilepsy. Front. Neurol. 2014, 5, 11. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Ohno, Y.; Tokudome, K. Therapeutic Role of Synaptic Vesicle Glycoprotein 2A (SV2A) in Modulating Epileptogenesis. CNS Neurol. Disord. Drgu Targets 2017, 16, 463–471. [Google Scholar] [CrossRef] [PubMed]
- Lyseng-Williamson, K.A. Levetiracetam: A Review of Its Use in Epilepsy. Drugs 2011, 71, 489–514. [Google Scholar] [CrossRef]
- Ando, S.; Funato, M.; Ohuchi, K.; Inagaki, S.; Sato, A.; Seki, J.; Kawase, C.; Saito, T.; Nishio, H.; Nakamura, S.; et al. The Protective Effects of Levetiracetam on a Human IPSCs-Derived Spinal Muscular Atrophy Model. Neurochem. Res. 2019, 44, 1773–1779. [Google Scholar] [CrossRef]
- Dircio-Bautista, M.; Colín-González, A.L.; Aguilera, G.; Maya-López, M.; Villeda-Hernández, J.; Galván-Arzate, S.; García, E.; Túnez, I.; Santamaría, A. The Antiepileptic Drug Levetiracetam Protects Against Quinolinic Acid-Induced Toxicity in the Rat Striatum. Neurotox. Res. 2018, 33, 837–845. [Google Scholar] [CrossRef] [PubMed]
- Negri, J.; Menon, V.; Young-Pearse, T.L. Assessment of Spontaneous Neuronal Activity In Vitro Using Multi-Well Multi-Electrode Arrays: Implications for Assay Development. eNeuro 2020, 7. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Xu, Z.; Song, Y.; Jiang, H.; Kong, Y.; Li, X.; Chen, J.; Wu, Y. Regeneration of Arrayed Gold Microelectrodes Equipped for a Real-Time Cell Analyzer. J. Vis. Exp. 2018, 133, 56250. [Google Scholar] [CrossRef] [PubMed]
- Odawara, A.; Matsuda, N.; Ishibashi, Y.; Yokoi, R.; Suzuki, I. Toxicological Evaluation of Convulsant and Anticonvulsant Drugs in Human Induced Pluripotent Stem Cell-Derived Cortical Neuronal Networks Using an MEA System. Sci. Rep. 2018, 8, 10416. [Google Scholar] [CrossRef]
- Di Baldassarre, A.; D’Amico, M.A.; Izzicupo, P.; Gaggi, G.; Guarnieri, S.; Mariggiò, M.A.; Antonucci, I.; Corneo, B.; Sirabella, D.; Stuppia, L.; et al. Cardiomyocytes Derived from Human CardiopoieticAmniotic Fluids. Sci. Rep. 2018, 8, 12028. [Google Scholar] [CrossRef] [PubMed]
- Mossink, B.; Verboven, A.H.A.; van Hugte, E.J.H.; Gunnewiek, T.M.K.; Parodi, G.; Linda, K.; Schoenmaker, C.; Kleefstra, T.; Kozicz, T.; van Bokhoven, H.; et al. Human Neuronal Networks on Micro-Electrode Arrays Are a Highly Robust Tool to Study Disease-Specific Genotype-Phenotype Correlations In Vitro. Stem Cell Rep. 2021, 16, 2182–2196. [Google Scholar] [CrossRef] [PubMed]
- Gold, C.; Henze, D.A.; Koch, C. Using Extracellular Action Potential Recordings to Constrain Compartmental Models. J. Comput. Neurosci. 2007, 23, 39–58. [Google Scholar] [CrossRef]
- Chiappalone, M.; Novellino, A.; Vajda, I.; Vato, A.; Martinoia, S.; van Pelt, J. Burst Detection Algorithms for the Analysis of Spatio-Temporal Patterns in Cortical Networks of Neurons. Neurocomputing 2005, 65–66, 653–662. [Google Scholar] [CrossRef]
- Obien, M.E.J.; Deligkaris, K.; Bullmann, T.; Bakkum, D.J.; Frey, U. Revealing Neuronal Function through Microelectrode Array Recordings. Front. Neurosci. 2015, 8, 423. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Bakkum, D.J.; Obien, M.E.J.; Radivojevic, M.; Jäckel, D.; Frey, U.; Takahashi, H.; Hierlemann, A. The Axon Initial Segment Is the Dominant Contributor to the Neuron’s Extracellular Electrical Potential Landscape. Adv. Biosys. 2019, 3, 1800308. [Google Scholar] [CrossRef] [PubMed]
- Müller, J.; Ballini, M.; Livi, P.; Chen, Y.; Radivojevic, M.; Shadmani, A.; Viswam, V.; Jones, I.L.; Fiscella, M.; Diggelmann, R.; et al. High-Resolution CMOS MEA Platform to Study Neurons at Subcellular, Cellular, and Network Levels. Lab Chip 2015, 15, 2767–2780. [Google Scholar] [CrossRef]
- Sergey, S.; David, J.; Andreas, H. Studying Extracellular Action Potential Waveforms Using HD MEAs. Front. Neurosci. 2016, 10, 130. [Google Scholar] [CrossRef]
- Ohara, R.; Imamura, K.; Morii, F.; Egawa, N.; Tsukita, K.; Enami, T.; Shibukawa, R.; Mizuno, T.; Nakagawa, M.; Inoue, H. Modeling Drug-Induced Neuropathy Using Human IPSCs for Predictive Toxicology. Clin. Pharmacol. Ther. 2017, 101, 754–762. [Google Scholar] [CrossRef]
- Kayama, T.; Suzuki, I.; Odawara, A.; Sasaki, T.; Ikegaya, Y. Temporally Coordinated Spiking Activity of Human Induced Pluripotent Stem Cell-Derived Neurons Co-Cultured with Astrocytes. Biochem. Biophys. Res. Commun. 2018, 495, 1028–1033. [Google Scholar] [CrossRef]
- Fukushima, K.; Miura, Y.; Sawada, K.; Yamazaki, K.; Ito, M. Establishment of a Human Neuronal Network Assessment System by Using a Human Neuron/Astrocyte Co-Culture Derived from Fetal Neural Stem/Progenitor Cells. J. Biomol. Screen 2016, 21, 54–64. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Frega, M.; van Gestel, S.H.C.; Linda, K.; van der Raadt, J.; Keller, J.; Van Rhijn, J.-R.; Schubert, D.; Albers, C.A.; Nadif Kasri, N. Rapid Neuronal Differentiation of Induced Pluripotent Stem Cells for Measuring Network Activity on Micro-Electrode Arrays. J. Vis. Exp. 2017, 119, 54900. [Google Scholar] [CrossRef] [Green Version]
- Bradley, J.A.; Luithardt, H.H.; Metea, M.R.; Strock, C.J. In Vitro Screening for Seizure Liability Using Microelectrode Array Technology. Toxicol. Sci. 2018, 163, 240–253. [Google Scholar] [CrossRef]
- Liu, J.; Sternberg, A.R.; Ghiasvand, S.; Berdichevsky, Y. Epilepsy-on-a-Chip System for Antiepileptic Drug Discovery. IEEE Trans. Biomed. Eng. 2019, 66, 1231–1241. [Google Scholar] [CrossRef] [PubMed]
- Gold, C.; Henze, D.A.; Koch, C.; Buzsáki, G. On the Origin of the Extracellular Action Potential Waveform: A Modeling Study. J. Neurophysiol. 2006, 95, 3113–3128. [Google Scholar] [CrossRef]
- Gaggi, G.; Di Credico, A.; Izzicupo, P.; Iannetti, G.; Di Baldassarre, A.; Ghinassi, B. Chemical and Biological Molecules Involved in Differentiation, Maturation, and Survival of Dopaminergic Neurons in Health and Parkinson’s Disease: Physiological Aspects and Clinical Implications. Biomedicines 2021, 9, 754. [Google Scholar] [CrossRef] [PubMed]
- Maury, Y.; Côme, J.; Piskorowski, R.A.; Salah-Mohellibi, N.; Chevaleyre, V.; Peschanski, M.; Martinat, C.; Nedelec, S. Combinatorial Analysis of Developmental Cues Efficiently Converts Human Pluripotent Stem Cells into Multiple Neuronal Subtypes. Nat. Biotechnol. 2015, 33, 89–96. [Google Scholar] [CrossRef]
- Gaggi, G.; Di Credico, A.; Izzicupo, P.; Sancilio, S.; Di Mauro, M.; Iannetti, G.; Dolci, S.; Amabile, G.; Di Baldassarre, A.; Ghinassi, B. Decellularized Extracellular Matrices and Cardiac Differentiation: Study on Human Amniotic Fluid-Stem Cells. Int. J. Mol. Sci. 2020, 21, 6317. [Google Scholar] [CrossRef] [PubMed]
- Li, L.; Chao, J.; Shi, Y. Modeling Neurological Diseases Using IPSC-Derived Neural Cells: IPSC Modeling of Neurological Diseases. Cell Tissue Res. 2018, 371, 143–151. [Google Scholar] [CrossRef]
- Di Baldassarre, A.; Cimetta, E.; Bollini, S.; Gaggi, G.; Ghinassi, B. Human-Induced Pluripotent Stem Cell Technology and Cardiomyocyte Generation: Progress and Clinical Applications. Cells 2018, 7, 48. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Gaggi, G.; Di Credico, A.; Izzicupo, P.; Alviano, F.; Di Mauro, M.; Di Baldassarre, A.; Ghinassi, B. Human Mesenchymal Stromal Cells Unveil an Unexpected Differentiation Potential toward the Dopaminergic Neuronal Lineage. Int. J. Mol. Sci. 2020, 21, 6589. [Google Scholar] [CrossRef] [PubMed]
- Gaggi, G.; Izzicupo, P.; Di Credico, A.; Sancilio, S.; Di Baldassarre, A.; Ghinassi, B. Spare Parts from Discarded Materials: Fetal Annexes in Regenerative Medicine. Int. J. Mol. Sci. 2019, 20, 1573. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Gaggi, G.; Di Credico, A.; Izzicupo, P.; Antonucci, I.; Crescioli, C.; Di Giacomo, V.; Di Ruscio, A.; Amabile, G.; Alviano, F.; Di Baldassarre, A.; et al. Epigenetic Features of Human Perinatal Stem Cells Redefine Their Stemness Potential. Cells 2020, 9, 1304. [Google Scholar] [CrossRef] [PubMed]
- Cavitt, J.; Privitera, M. Levetiracetam Induces a Rapid and Sustained Reduction of Generalized Spike-Wave and Clinical Absence. Arch. Neurol. 2004, 61, 1604. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Lynch, B.A.; Lambeng, N.; Nocka, K.; Kensel-Hammes, P.; Bajjalieh, S.M.; Matagne, A.; Fuks, B. The Synaptic Vesicle Protein SV2A Is the Binding Site for the Antiepileptic Drug Levetiracetam. Proc. Natl. Acad. Sci. USA 2004, 101, 9861–9866. [Google Scholar] [CrossRef] [Green Version]
- Yang, X.-F.; Rothman, S.M. Levetiracetam Has a Time- and Stimulation-Dependent Effect on Synaptic Transmission. Seizure 2009, 18, 615–619. [Google Scholar] [CrossRef] [Green Version]
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. |
© 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
Share and Cite
Di Credico, A.; Gaggi, G.; Izzicupo, P.; Ferri, L.; Bonanni, L.; Iannetti, G.; Di Baldassarre, A.; Ghinassi, B. Real-Time Monitoring of Levetiracetam Effect on the Electrophysiology of an Heterogenous Human iPSC-Derived Neuronal Cell Culture Using Microelectrode Array Technology. Biosensors 2021, 11, 450. https://doi.org/10.3390/bios11110450
Di Credico A, Gaggi G, Izzicupo P, Ferri L, Bonanni L, Iannetti G, Di Baldassarre A, Ghinassi B. Real-Time Monitoring of Levetiracetam Effect on the Electrophysiology of an Heterogenous Human iPSC-Derived Neuronal Cell Culture Using Microelectrode Array Technology. Biosensors. 2021; 11(11):450. https://doi.org/10.3390/bios11110450
Chicago/Turabian StyleDi Credico, Andrea, Giulia Gaggi, Pascal Izzicupo, Laura Ferri, Laura Bonanni, Giovanni Iannetti, Angela Di Baldassarre, and Barbara Ghinassi. 2021. "Real-Time Monitoring of Levetiracetam Effect on the Electrophysiology of an Heterogenous Human iPSC-Derived Neuronal Cell Culture Using Microelectrode Array Technology" Biosensors 11, no. 11: 450. https://doi.org/10.3390/bios11110450