Dietary exposure to plasmenylethanolamine prevents microglia-mediated neuroinflammation by enhancing microglia autophagy

Abstract

Microglia-mediated neuroinflammation plays a central role in the pathology of Alzheimer's disease (AD). Hence, regulation of microglia-mediated neuroinflammation could be a valuable strategy in preventing or treating AD. Great efforts have been put in demonstrating the effect of plasmenylethanolamine (PlsEtn) supplementation, a natural nutrient, on the treatment of neurodegenerative disease. However, the potential regulation of neuroinflammatory responses in the brain by PlsEtn has not been comprehensively examined. APPswe/PSEN1dE9 (APP/PS1) mice was used in this study, and these mice were administered PlsEtn orally (0.1% w/w in Chow diet) for 20 weeks. SH-SY5Y cells was cultured with the conditioned medium (CM) from lipopolysaccharides-treated or plasmenylethanolamine-treated BV2 microglia. We showed that treatment with PlsEtn ameliorated neuronal loss against microglial activation in APP/PS1 mice and SH-SY5Y cells. Further study revealed that PlsEtn promotes microglial autophagy and attenuates proinflammatory response in BV2 microglial cells exposed to lipopolysaccharide (LPS). Of note, plasmenylethanolamine-induced restoration of autophagy contributes to the inhibition of LPS-induced neuroinflammation and improvement of neuronal activity. Inhibition of microglial autophagy with 3-Methyladenine partly blunted the inhibitory effect on LPS-induced neuroinflammation and neuroprotective effects of PlsEtn, which suggested that promotion of microglial autophagy accounted for the anti-neuroinflammatory and neuroprotective actions of PlsEtn. Together, our study purports the microglia autophagy as a mechanism for the potential of PlsEtn to attenuate neuroinflammation and neuron loss.