Electrochemical Probing of Dopamine Dynamics During Poly(I:C)-Induced Neuroinflammation

Abstract

Viruses can infiltrate the central nervous system and contribute to depression, which may include alterations in dopamine (DA) metabolism triggered by immune responses though the specific mechanisms involved remain unclear. Here, an electrochemical system to realize the real-time dynamic monitoring of DA with high sensitivity is proposed and it is demonstrated that the viral simulator polyinosinic-polycytidylic acid (poly(I:C)) can inhibit the release of DA (from 5.595 to 0.137 µm) in neurons from the perspective of single cells, cell populations and even in vivo through the combination of multiscale electrodes, including single nanowires, carbon fibers (CFs) and 2D flexible electrodes. These findings are associated with the increase in reactive oxygen species (ROS) produced by microglia. At the molecular level, poly(I:C) significantly decreases the expression of α-synuclein and increases its phosphorylation level, whereas ROS inhibitors can reverse these pathological changes and salvage DA release to half the initial level (≈2.6 µM). These results suggest that viruses may indirectly inhibit DA system function through ROS produced in inflammatory responses and that antioxidant activity may be a potential therapeutic strategy.