Restoring Oat Nanoparticles Mediated Brain Memory Function of Mice Fed Alcohol by Sorting Inflammatory Dectin-1 Complex Into Microglial Exosomes

Microglia modulate pro-inflammatory and neurotoxic activities. Edible plantderived factors improve brain function. Current knowledge of the molecular interactions between edible plant-derived factors and the microglial cell is limited. Here an alcohol-induced chronic brain inflammation model is used to identify that the microglial cell is the novel target of oat nanoparticles (oatN). Oral administration of oatN inhibits brain inflammation and improves brain memory function of mice that are fed alcohol. Mechanistically, ethanol activates dectin-1 mediated inflammatory pathway. OatN is taken up by microglial cells via beta-glucan mediated binding to microglial hippocalcin (HPCA) whereas oatN digalactosyldiacylglycerol (DGDG) prevents assess of oatN beta-glucan to dectin-1. Subsequently endocytosed beta-glucan/HPCA is recruited in an endosomal recycling compartment (ERC) via interaction with Rablla. This complex then sequesters the dectin-1 in the ERC in an oatN beta-glucan dependent manner and alters the location ofdectin-1 from Golgi to early endosomes and lysosomes and increases exportation of dectin-1 into exosomes in an Rablla dependent manner. Collectively, these cascading actions lead to preventing the activation of the alcoholic induced brain inflammation signing pathway(s). This coordinated assembling of the HPCA/Rablla/dectin-1 complex by oral administration of oatN may contribute to the prevention of brain inflammation.