Sleep deprivation aggravates lipopolysaccharide-induced anxiety, depression and cognitive impairment: The role of pro-inflammatory cytokines and synaptic plasticity-associated proteins

Growing evidence indicates that neuroinflammation plays a critical role in anxiety, depression, and cognitive impairment. Sleep loss disrupts the host's immune balance and increases neuroinflammation. This study explored whether chronic sleep deprivation aggravates lipopolysaccharide-induced anxiety, depression, and cognitive impairment and assessed the underlying mechanisms. Lipopolysaccharide (250 μg/kg) was administered to adult mice for 9 days, accompanied with daily intermittent sleep deprivation from 12:00 to 18:00 by using an activity wheel. Anxiety, depression, and cognitive function were evaluated using a task battery consisting of an open field, elevated plus maze, tail suspension, forced swimming, and Morris water maze tests. The levels of pro-inflammatory cytokines and synaptic plasticity-associated proteins were examined by enzyme-linked immunosorbent assay and western blot, respectively. The results showed that lipopolysaccharide increased anxiety- and depression-like behaviors, impaired cognitive function, uprelated interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α), and decreased brain-derived neurotrophic factor (BDNF), postsynaptic density-95 (PSD-95), and synaptophysin (SYN), which were aggravated by chronic sleep deprivation. These results suggest that chronic sleep deprivation exerted adverse effects on lipopolysaccharide-induced anxiety, depression, and cognitive impairment, which was associated with changes in pro-inflammatory cytokines and synaptic plasticity associated proteins.