【Animal Modeling】-Knockout of Leptin Receptor Causes Activation of Microglia in Rat Brain Tissue

  Objective To analyze the morphological and functional changes of microglia in the brain of leptin receptor (LEPR) knockout rats, and to explore the function of leptin receptor in microglia. effect.

  Methods RT-PCR, Western blotting, immunohistochemistry and immunofluorescence were used to observe the activation state of microglia in vitro and in vivo after rat leptin receptor knockout.

  Results Leptin receptor was expressed in microglia, and gene knockout could completely eliminate LEPR protein in microglia; LEPR knockout enhanced the inflammatory response of rat LPS to stimulation, and the survival rate decreased by 75%; The proportion of activated microglia in the mouse brain was significantly increased; LEPR knockout primary microglia not only secreted more inflammatory factors but also enhanced phagocytic ability; Western blot found that PI3K/AKT in leptin receptor knockout The phosphorylation of rat brain tissue protein was significantly enhanced.

  Conclusion After leptin receptor knockout, rat microglia develop towards pro-inflammatory and pro-phagocytic direction, revealing that LEPR/Leptin may regulate neuroinflammation through microglia.