The effect of pharmacological inhibition of Serine Proteases on neuronal networks in vitro

PeerJ

article

Sebastiaan Van De Vijver¹  Stephan Missault²  Jeroen Van Soom³  Pieter Van Der Veken³  Koen Augustyns³  Jurgen Joossens³  Stefanie Dedeurwaerdere⁴  Michele Giugliano¹ 

[1] Molecular, Cellular, and Network Excitability, Department of Biomedical Sciences and Institute Born-Bunge, University of Antwerp;Experimental Laboratory of Translational Neuroscience and Otolaryngology, Department of Translational Neurosciences, University of Antwerp;Laboratory of Medicinal Chemistry, Department of Pharmaceutical Sciences, University of Antwerp;Laboratory of Experimental Haematology, VAXINFECTIO, University of Antwerp;Neuroscience sector

关键词: Extracellular matrix;    Microelectrode arrays;    Neurons;    Network activity;    Serine proteases;    Patch-clamp;    Cortex;    Electrophysiology;    Synaptic connectivity;    Neurobiology;   

DOI  :  10.7717/peerj.6796

学科分类：社会科学、人文和艺术（综合）

来源: Inra

【 摘 要 】

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.

【 授权许可】

CC BY