earticle

영어

Sleep is an evolutionarily conserved physiological process implicated in the consolidation of learning and memory (L/M). Here, we hypothesize that sleep deprivation (SD)-induced cognitive deficits in zebrafish and mouse are mediated through reduction in O-GlcNAcylation in the brain. At the molecular level, SD downregulated mRNA of key enzymes of HBP metabolism and O-GlcNAc transferase (OGT) along with increased O-GlcNAcase (OGA) expression. Fear conditioning (FC) induced an increase in the expression or activities of proteins associated with long term memory (LTM), and at the same time, OGT protein and O-GlcNAcylation were significantly increased in the normalbut not in the SD-group of zebrafish. Suppression of HBP by the GFAT inhibitor, diazo-oxo-norleucine (DON), impaired L/M function and FC-mediated activation of PKA/CREB signaling. Conversely, enhancement of HBP by glucosamine significantly restored cognitive deficits and increased PKA/CREB signaling in the SD group. To our knowledge, the current study has provided valuable insights into the molecular and biochemical changes associated with L/M at the whole-brain level using the zebrafish and mouse system for the first time. Our findings highlight the role of the HBP during the L/M process and provide potential therapeutic targets for cognitive defects.