The effect of pharmacological inhibition of Serine Proteases on neuronal networks in vitro
Sebastiaan Van De Vijver,
Stephan Missault,
Jeroen Van Soom,
Pieter Van Der Veken,
Koen Augustyns,
Jurgen Joossens,
Stefanie Dedeurwaerdere,
Michele Giugliano
Affiliations
Sebastiaan Van De Vijver
Molecular, Cellular, and Network Excitability, Department of Biomedical Sciences and Institute Born-Bunge, University of Antwerp, Wilrijk, Flanders, Belgium
Stephan Missault
Experimental Laboratory of Translational Neuroscience and Otolaryngology, Department of Translational Neurosciences, University of Antwerp, Wilrijk, Flanders, Belgium
Jeroen Van Soom
Laboratory of Medicinal Chemistry, Department of Pharmaceutical Sciences, University of Antwerp, Wilrijk, Flanders, Belgium
Pieter Van Der Veken
Laboratory of Medicinal Chemistry, Department of Pharmaceutical Sciences, University of Antwerp, Wilrijk, Flanders, Belgium
Koen Augustyns
Laboratory of Medicinal Chemistry, Department of Pharmaceutical Sciences, University of Antwerp, Wilrijk, Flanders, Belgium
Jurgen Joossens
Laboratory of Medicinal Chemistry, Department of Pharmaceutical Sciences, University of Antwerp, Wilrijk, Flanders, Belgium
Stefanie Dedeurwaerdere
Laboratory of Experimental Haematology, VAXINFECTIO, University of Antwerp, Wilrijk, Flanders, Belgium
Michele Giugliano
Molecular, Cellular, and Network Excitability, Department of Biomedical Sciences and Institute Born-Bunge, University of Antwerp, Wilrijk, Flanders, Belgium
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.
