Krill oil attenuates diabetes-associated cognitive dysfunction by inhibiting microglial polarization-induced neuron injury

Increasing attention has been paid to diabetes-associated cognitive dysfunction (DCD) due to its high prevalence and severe impact on life quality in the diabetic population. However, effective interventions for DCD currently are limited. In this study, we investigated the preventive effect of krill oil (KO) on DCD using a mouse model of type 2 diabetes induced by streptozotocin and high-fat diet. The diabetic mice developed cognitive impairment, as well as neuron loss, oxidative stress and inflammation in the hippocampi, the effects of which were significantly prevented by KO. Cell experiments found that KO did not offer a direct protection against advanced glycation end products-induced neuronal activation of apoptotic signaling pathway and neuron loss. In contrast, KO remarkably inactivated the M1 polarized microglia induced by lipopolysaccharide, the effect of which mitigated apoptosis of co-cultured neurons. In M1 polarized microglia, KO predominantly inhibited inflammation and oxidative stress pathways as revealed by RNA-sequencing. These effects were further confirmed in M1 polarized microglia by the KO-decreased expression of inflammatory and oxidative genes, as well as reactive oxygen species level. The current study reported that KO improved DCD through inactivation of microglia, providing a potential effective approach for the intervention of DCD.