SELENOM Knockout Induces Synaptic Deficits and Cognitive Dysfunction by Influencing Brain Glucose Metabolism

Abstract

Selenium, a trace element associated with memory impairment and glucose metabolism, mainly exerts its function through selenoproteins. SELENOM is a selenoprotein located in the endoplasmic reticulum (ER) lumen. Our study demonstrates for the first time that SELENOM knockout decreases synaptic plasticity and causes memory impairment in 10-month-old mice. In addition, SELENOM knockout causes hyperglycaemia and disturbs glucose metabolism, which is essential for synapse formation and transmission in the brain. Further research reveals that SELENOM knockout leads to inhibition of the brain insulin signaling pathway [phosphatidylinositol 3-kinase (PI3K)/AKT/mTOR/p70 S6 kinase pathway], which may impair synaptic plasticity in mice. High-fat diet (HFD) feeding suppresses the brain insulin signaling pathway in SELENOM knockout mice and leads to earlier onset of cognitive impairment at 5 months of age. In general, our study demonstrates that SELENOM knockout induces synaptic deficits via the brain insulin signaling pathway, thus leading to cognitive dysfunction in mice. These data strongly suggest that SELENOM plays a vital role in brain glucose metabolism and contributes substantially to synaptic plasticity.

Keywords: SELENOM; cognitive dysfunction; glucose metabolism.