Effect of Selenium Treatment on Central Insulin Sensitivity: A Proteomic Analysis in β-Amyloid Precursor Protein/Presenilin-1 Transgenic Mice

Abstract

Prior studies have demonstrated a close association between brain insulin resistance and Alzheimer’s disease (AD), while selenium supplementation was shown to improve insulin homeostasis in AD patients and to exert neuroprotective effects in a mouse model of AD. However, the mechanisms underlying the neuroprotective actions of selenium remain incompletely understood. In this study, we performed a label-free liquid chromatography-tandem mass spectrometry (LC–MS/MS) quantitative proteomics approach to analyze differentially expressed proteins (DEPs) in the hippocampus and cerebral cortex of Aβ precursor protein (APP)/presenilin-1 (PS1) mice following 2 months of treatment with sodium selenate. A total of 319 DEPs (205 upregulated and 114 downregulated proteins) were detected after selenium treatment. Functional enrichment analysis revealed that the DEPs were mainly enriched in processes affecting axon development, neuron differentiation, tau protein binding, and insulin/insulin-like growth factor type 1 (IGF1)-related pathways. These results demonstrate that a number of insulin/IGF1 signaling pathway-associated proteins are differentially expressed in ways that are consistent with reduced central insulin resistance, suggesting that selenium has therapeutic value in the treatment of neurodegenerative and metabolic diseases such as AD and non-alcoholic fatty liver disease (NAFLD).