Van De Vijver Sebastiaan, Missault Stephan, Van Soom Jeroen, Van Der Veken Pieter, Augustyns Koen, Joossens Jurgen, Dedeurwaerdere Stefanie, Giugliano Michele
Molecular, Cellular, and Network Excitability, Department of Biomedical Sciences and Institute Born-Bunge, University of Antwerp, Wilrijk, Flanders, Belgium.
Experimental Laboratory of Translational Neuroscience and Otolaryngology, Department of Translational Neurosciences, University of Antwerp, Wilrijk, Flanders, Belgium.
PeerJ. 2019 Apr 23;7:e6796. doi: 10.7717/peerj.6796. eCollection 2019.
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 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.
神经元嵌入细胞外基质（ECM）中，该基质既作为支架发挥作用，又作为神经元功能的调节器。反过来，ECM通过丝氨酸蛋白酶的作用而动态改变，丝氨酸蛋白酶会分解其成分。这条途径与突触可塑性和神经元内在兴奋性的调节有关。在本研究中，我们使用新开发的丝氨酸蛋白酶抑制剂，确定了干扰ECM中蛋白水解过程的短期影响。我们使用微电极阵列监测原代大鼠皮质培养物的自发电生理活动。虽然低剂量的药物抑制没有显著影响，但在高浓度时，它会显著改变网络同步性和功能连接性，但单细胞电特性保持不变。这些结果表明，丝氨酸蛋白酶抑制可能通过其对ECM的作用影响突触特性。
