Fig. 9

Schematic showing that PRL deficiency drives diabetes-associated cognitive dysfunction by enhancing microglia-mediated synaptic engulfment. PRL modulates hippocampal synaptic density by regulating the microglial phagocytic ability to synapses for maintenance of normal cognitive function. In diabetes, PRL deficiency drives cognitive decline and hippocampal synaptic loss by enhancing microglial engulfment of synapses. Mechanistically, PRL diminishing promotes Rap1 activation by upregulating expression of RapGEFs, which in turn enhances microglial phagocytic ability