Details

Autor(en) / Beteiligte

• Xu, Fangyi
• Mu, Jingyao
• Teng, Yun
• Zhang, Xiangcheng
• Sundaram, Kumaran
• Sriwastva, Mukesh K.
• Kumar, Anil
• Lei, Chao
• Zhang, Lifeng
• Liu, Qiaohong M.
• Yan, Jun
• McClain, Craig J.
• Merchant, Michael L.
• Zhang, Huang‐Ge

Titel

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

Ist Teil von

• Small (Weinheim an der Bergstrasse, Germany), 2022-02, Vol.18 (6), p.e2105385-n/a

Ort / Verlag

Germany: Wiley Subscription Services, Inc

Erscheinungsjahr

2022

Quelle

Wiley Online Library All Journals

Beschreibungen/Notizen

• Microglia modulate pro‐inflammatory and neurotoxic activities. Edible plant‐derived 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 β‐glucan mediated binding to microglial hippocalcin (HPCA) whereas oatN digalactosyldiacylglycerol (DGDG) prevents assess of oatN β‐glucan to dectin‐1. Subsequently endocytosed β‐glucan/HPCA is recruited in an endosomal recycling compartment (ERC) via interaction with Rab11a. This complex then sequesters the dectin‐1 in the ERC in an oatN β‐glucan dependent manner and alters the location of dectin‐1 from Golgi to early endosomes and lysosomes and increases exportation of dectin‐1 into exosomes in an Rab11a 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/Rab11a/dectin‐1 complex by oral administration of oatN may contribute to the prevention of brain inflammation. In this article, oral administration of oat nanoparticles (OatN) is trafficking to brain and inhibits microglial dectin‐1 mediated inflammation and memory loss in a mouse alcohol use disorder model. OatN beta‐glucan targets to microglial cells and subsequent interaction with hippocalcin whereas oatN digalactosyldiacylglycerol prevents oatN b‐glucan accessing to dectin‐1, leading to prevention of dectin‐1 mediated activation of inflammation pathway.