The effect of pharmacological inhibition of Serine Proteases on neuronal networks in vitro
Neurons are embedded in an extracellular matrix (ECM), which functions both as a scaffold and as a regulator of neuronal function. The ECM is in turn dynamically altered through the action of serine proteases, which break down its constituents. This pathway has been implicated in the regulation of s...
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PeerJ Inc.
2019-04-01
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author | Sebastiaan Van De Vijver Stephan Missault Jeroen Van Soom Pieter Van Der Veken Koen Augustyns Jurgen Joossens Stefanie Dedeurwaerdere Michele Giugliano |
author_facet | Sebastiaan Van De Vijver Stephan Missault Jeroen Van Soom Pieter Van Der Veken Koen Augustyns Jurgen Joossens Stefanie Dedeurwaerdere Michele Giugliano |
author_sort | Sebastiaan Van De Vijver |
collection | DOAJ |
description | Neurons are embedded in an extracellular matrix (ECM), which functions both as a scaffold and as a regulator of neuronal function. The ECM is in turn dynamically altered through the action of serine proteases, which break down its constituents. This pathway has been implicated in the regulation of synaptic plasticity and of neuronal intrinsic excitability. In this study, we determined the short-term effects of interfering with proteolytic processes in the ECM, with a newly developed serine protease inhibitor. We monitored the spontaneous electrophysiological activity of in vitro primary rat cortical cultures, using microelectrode arrays. While pharmacological inhibition at a low dosage had no significant effect, at elevated concentrations it altered significantly network synchronization and functional connectivity but left unaltered single-cell electrical properties. These results suggest that serine protease inhibition affects synaptic properties, likely through its actions on the ECM. |
first_indexed | 2024-03-09T06:32:04Z |
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institution | Directory Open Access Journal |
issn | 2167-8359 |
language | English |
last_indexed | 2024-03-09T06:32:04Z |
publishDate | 2019-04-01 |
publisher | PeerJ Inc. |
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series | PeerJ |
spelling | doaj.art-7fadd74250a346db96f04537f7b045152023-12-03T11:04:34ZengPeerJ Inc.PeerJ2167-83592019-04-017e679610.7717/peerj.6796The effect of pharmacological inhibition of Serine Proteases on neuronal networks in vitroSebastiaan Van De Vijver0Stephan Missault1Jeroen Van Soom2Pieter Van Der Veken3Koen Augustyns4Jurgen Joossens5Stefanie Dedeurwaerdere6Michele Giugliano7Molecular, Cellular, and Network Excitability, Department of Biomedical Sciences and Institute Born-Bunge, University of Antwerp, Wilrijk, Flanders, BelgiumExperimental Laboratory of Translational Neuroscience and Otolaryngology, Department of Translational Neurosciences, University of Antwerp, Wilrijk, Flanders, BelgiumLaboratory of Medicinal Chemistry, Department of Pharmaceutical Sciences, University of Antwerp, Wilrijk, Flanders, BelgiumLaboratory of Medicinal Chemistry, Department of Pharmaceutical Sciences, University of Antwerp, Wilrijk, Flanders, BelgiumLaboratory of Medicinal Chemistry, Department of Pharmaceutical Sciences, University of Antwerp, Wilrijk, Flanders, BelgiumLaboratory of Medicinal Chemistry, Department of Pharmaceutical Sciences, University of Antwerp, Wilrijk, Flanders, BelgiumLaboratory of Experimental Haematology, VAXINFECTIO, University of Antwerp, Wilrijk, Flanders, BelgiumMolecular, Cellular, and Network Excitability, Department of Biomedical Sciences and Institute Born-Bunge, University of Antwerp, Wilrijk, Flanders, BelgiumNeurons are embedded in an extracellular matrix (ECM), which functions both as a scaffold and as a regulator of neuronal function. The ECM is in turn dynamically altered through the action of serine proteases, which break down its constituents. This pathway has been implicated in the regulation of synaptic plasticity and of neuronal intrinsic excitability. In this study, we determined the short-term effects of interfering with proteolytic processes in the ECM, with a newly developed serine protease inhibitor. We monitored the spontaneous electrophysiological activity of in vitro primary rat cortical cultures, using microelectrode arrays. While pharmacological inhibition at a low dosage had no significant effect, at elevated concentrations it altered significantly network synchronization and functional connectivity but left unaltered single-cell electrical properties. These results suggest that serine protease inhibition affects synaptic properties, likely through its actions on the ECM.https://peerj.com/articles/6796.pdfExtracellular matrixMicroelectrode arraysNeuronsNetwork activitySerine proteasesPatch-clamp |
spellingShingle | Sebastiaan Van De Vijver Stephan Missault Jeroen Van Soom Pieter Van Der Veken Koen Augustyns Jurgen Joossens Stefanie Dedeurwaerdere Michele Giugliano The effect of pharmacological inhibition of Serine Proteases on neuronal networks in vitro PeerJ Extracellular matrix Microelectrode arrays Neurons Network activity Serine proteases Patch-clamp |
title | The effect of pharmacological inhibition of Serine Proteases on neuronal networks in vitro |
title_full | The effect of pharmacological inhibition of Serine Proteases on neuronal networks in vitro |
title_fullStr | The effect of pharmacological inhibition of Serine Proteases on neuronal networks in vitro |
title_full_unstemmed | The effect of pharmacological inhibition of Serine Proteases on neuronal networks in vitro |
title_short | The effect of pharmacological inhibition of Serine Proteases on neuronal networks in vitro |
title_sort | effect of pharmacological inhibition of serine proteases on neuronal networks in vitro |
topic | Extracellular matrix Microelectrode arrays Neurons Network activity Serine proteases Patch-clamp |
url | https://peerj.com/articles/6796.pdf |
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