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

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.

Automated summary

The study demonstrates that plasmenylethanolamine (PlsEtn) attenuates neuroinflammation and neuronal loss by promoting microglial autophagy. This finding may contribute to the prevention and treatment of Alzheimer's disease.