Inflammatory Molecules Released by Mechanically Injured Astrocytes Trigger Presynaptic Loss in Cortical Neuronal Networks

• DOI: 10.1021/acschemneuro.1c00488
• Publication Date: 2021-10-07T04:27:18Z
• Authors: Joséphine Lantoine; Anthony Procès; Agnès Villers; Sophie Halliez; Luc Buée; Laurence Ris; Sylvain Gabriele
• Keywords: Proinflammatory cytokine

Deformation, compression, or stretching of brain tissues cause diffuse axonal injury (DAI) and induce structural functional alterations astrocytes, the most abundant cell type in brain. To gain further insight into role mechanically activated astrocytes on neuronal networks, this study was designed to investigate whether cytokines released by can affect growth synaptic connections cortical networks. Astrocytes were cultivated elastic membranes subjected repetitive mechanical insults, whereas well-defined protein micropatterns used form standardized GFAP staining showed that after two cycles stretch mesoscale discovery assays indicated injured four major cytokines. understand these cytokines, networks cultured with supernatant healthy individual contribution proinflammatory cytokine tumor necrosis factor-α (TNF-α) studied. We found two-cycle stretched decreased presynaptic terminals TNF-α must be considered a key player loss. Furthermore, our results indicate significantly modulate balance between TNFR1 TNFR2 receptors enhancing R2 receptors. demonstrated is not involved process, suggesting predominant other secreted Together, contribute better understanding consequences astrocyte deformations highlight inflammatory signaling pathways plasticity modulation