Repetitive Exposure to Bacterial Endotoxin LPS Alters Synaptic Transmission

摘要

Background and Objective: Gram-negative bacteria produce and release endotoxins in the form of lipopolysaccharides (LPS), which can have direct effects on neural synaptic communication. Since the effects of acute repetitive exposures of LPS have not been fully addressed previously, the objective of this study was to investigate the repetitive effects of acute applications of LPS on synaptic transmission. Materials and Methods: The membrane potential of cells and the amplitude of evoked synaptic responses were measured with intracellular recordings. The larval Drosophila neuromuscular junction was used as a glutamatergic synaptic model. Results: LPS depressed synaptic transmission in a dose-dependent manner. LPS blocked the glutamate receptors while hyperpolarizing the postsynaptic cell. LPS induced hyperpolarization desensitized the cell to the effects of subsequent exposures to LPS. The responses from repeating short one minute exposures to LPS with 5 min of removal and washing with saline were reproducible over three trials. Over twenty minutes of incubation with LPS, the muscle fibers depolarized and did not recover with the removal of LPS as well as the glutamatergic synaptic responses. Conclusion: LPS directly blocks glutamatergic synaptic transmission. Cells can recover from rapid exposures to LPS within 1 min. Longer than 5 min of LPS exposure produces long term irreversible effects. Additive effects with low to higher concentrations of LPS occur. The mechanism of LPS hyperpolarizing skeletal muscle is unknown but occurs in larval Drosophila muscle.