Prolonged sleep deprivation induces cardiac dysfunction via microglia-neural circuit coupling

Most animals require sleep, and sleep deprivation(SD) can lead to severe pathophysiological consequences, including cardiac dysfunction and death. Substantial evidence shows that sleep deprivation impairs cardiac function and increases cardiovascular risk and whether sleep deprivation-mediated neural output exacerbates the deterioration of heart function. Here, we demonstrate how sleep deprivation induces symptoms of cardiac dysfunction. Sleep disruption following SD leads to impaired cardiac function. Prolonged sleep deprivation triggers rapid microglial recruitment to the fastigial nucleus (FN) of the cerebellum and enhances the phagocytic capacity of microglia toward dendritic spines of GABAergic neurons. Prolonged sleep deprivation enhances microglial activity in the FN of male mice. Concurrently, microglial engulfment of GABAergic neuronal dendritic spines suppresses GABA neuron activity, leading to increased cardiac sympathetic outflow through the FN ^GABA -RVLM circuit to the cardiac and ultimately inducing cardiac dysfunction.These findings reveal that prolonged sleep deprivation triggers dysregulated microglial phagocytosis, which functionally encodes impaired GABAergic neuron-mediated suppression of cardiac sympathetic outflow, thereby driving the progression of cardiac dysfunction following prolonged sleep loss.