Oxidative stress is associated with A accumulation in chronic sleep deprivation model

Amyloid-beta (A beta) accumulation is the main pathological change in Alzheimer's disease (AD), which results from the imbalance of production and clearance of A beta in the brain. Our previous study found that chronic sleep deprivation (CSD) led to the deposition of A beta in the brain by disrupting the balance of A beta production and clearance, but the specific mechanism was not clear. In the present study, we investigated the effects of oxidative stress on A beta accumulation in CSD rats. We found that the levels of reactive oxygen species (ROS) and malondialdehyde (MDA) significantly increased after CSD, while superoxide dismutase (SOD) decreased in the brain. Furthermore, the serum ROS was elevated and SOD declined after CSD. The levels of oxidative stress in the brain were significantly correlated with beta-site APP-cleaving enzyme 1 (BACE1), low-density lipoprotein receptorrelated protein-1 (LRP1), and receptor of advanced glycation end products (RAGE) levels in hippocampus and prefrontal lobe, and the concentration of serum oxidative mediators were strongly correlated with plasma levels of soluble LRP1 (sLRP1) and soluble RAGE (sRAGE). These results suggested that the oxidative stress in the brain and serum may involved in the CSD-induced A beta accumulation. The underlying mechanism may be associated with disrupting the balance of A beta production and clearance.