Reduction of eEF2 kinase alleviates the learning and memory impairment caused by acrylamide

Abstract

Abstract The impact of acrylamide (ACR) on learning and memory has garnered considerable attention. However, the targets and mechanisms are still unclear. We used proteomics technology to analyze the serum of the ACR occupationally exposed population and screen out target proteins related to learning and memory. Through in vivo, in vitro experiments, and transgenic mouse models, we investigated the selected target protein to elucidate. Elongation factor 2 (eEF2) was significantly upregulated in the results of serum proteomic. Results from in vitro and in vivo experiments indicated a notable upregulation of Eukaryotic elongation factor 2 kinase (eEF2K), the sole kinase responsible for eEF2 phosphorylation, following exposure to ACR (P < 0.05). Subsequent in vitro experiments using eEF2K siRNA and in vivo experiments with eEF2K-knockout mice demonstrated significant improvements in abnormal indicators related to ACR-induced learning and memory deficits (P < 0.05). Proteomic analysis of the hippocampus revealed Lpcat1 as a crucial downstream protein regulated by eEF2K. KEGG analysis indicated that eEF2K may play a role in the process of ACR-induced learning and memory impairment by affecting ether lipid metabolism. In summary, eEF2K as a pivotal target in the mechanisms underlying ACR-induced learning and memory impairment, providing robust evidence for potential clinical interventions targeting.