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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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Detalles Bibliográficos
Autores principales: Van De Vijver, Sebastiaan, Missault, Stephan, Van Soom, Jeroen, Van Der Veken, Pieter, Augustyns, Koen, Joossens, Jurgen, Dedeurwaerdere, Stefanie, Giugliano, Michele
Formato: Online Artículo Texto
Lenguaje:English
Publicado: PeerJ Inc. 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6485206/
https://www.ncbi.nlm.nih.gov/pubmed/31065460
http://dx.doi.org/10.7717/peerj.6796
Descripción
Sumario: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.