Study the role of extracellular vesicles in exercise-induced anti-microglial activation

  • 周 鴻霖

Student thesis: Doctoral Thesis

Abstract

Background: Exercise exerts multiple beneficial effects against chronic diseases but the detailed molecular mechanism is unclear It has been suggested that the anti-inflammatory effect contributes to a major part of the exercise benefit Previous studies have showed that extracellular vesicles (EVs) including exosomes and microvesicles secreted by cells into circulation playing important roles in long-distance intercellular communication We hypothesize that the exercise-derived EVs contribute to the exercise-induced anti-inflammatory effects Objective: To examine the anti-inflammatory effect of exosomes after long-term exercise training Methods: Male SD rats 7-week old were subjected to 1-hour and 4-week treadmill running Their plasma specimens were harvested immediately or 2-day after exercise The concentration and size distribution of EVs in the plasma were analyzed by Nanoparticles tracking analysis A combination of centrifugation and polymer-based precipitation method was used to isolate the exosomes The anti-inflammatory effect of exosomes were examined in vitro using macrophage/microglia cell line BV2 and in vivo in LPS-challenged mice Results: The concentrations of EVs were increased in the plasma of both 1-hour and 4-week exercised rats Using DiI-labeled exosomes we showed that exosomes could be absorbed by BV2 cells within 2 hours Pretreatment of exosomes for 2 hours inhibited LPS-induced activations of NFκB in the BV2 cell which was more pronounced in the exosomes derived from the 4-week exercise group Furthermore 2-hour after tail vein injection labeled exosomes could be identified in the brain parenchyma Exosomes derived from rats received 4-week exercise ameliorated the LPS-induced microglial activation in the substantia nigra Conclusion: Running exercise increase the concentration of EVs in the plasma Exosomes derived from long-term exercised rats possess anti-inflammatory effects Exercise alters the quantity and quality of EVs
Date of Award2019
Original languageEnglish
SupervisorYu-Min Kuo (Supervisor)

Cite this

'