Effects of chronic and repeated short-term sleep restriction (CRSR) on lipopolysaccharide (LPS)-induced cognitive deficits, anxiety-like behavior, and systemic inflammation. (A) Experimental schematic. Adult mice were subjected to CRSR consisting of 3 repeated cycles of 7-day sleep restriction with an interval of 7 days. LPS (5 mg/kg) or 0.9% saline (5 mL/kg) was administrated intraperitoneally 14 days after the last cycle of sleep restriction. In the Y maze test (YMT), the number of entries (B) and time spent in the novel arm (C) were assessed in each group 1 day prior to LPS treatment as a baseline and 2 days after LPS treatment. LPS-induced decreases in the number of entries and time spent in the novel arm were exaggerated by CRSR. In the OFT, time spent in the center (D) and freezing time (E) were assessed in each group 1 day prior to LPS treatment as a baseline and 2 days after LPS treatment. LPS-induced decreases in time spent in the center and freezing time were exaggerated by CRSR. Plasma was collected 24 hours after LPS treatment for enzyme linked immunosorbent assay (ELISA) detection of TNF-α (F), IL-6 (G), IL-17A (H) and IFN-γ (I) in each group. LPS-induced increases in hippocampal TNF-α, IL-6, IL-17A, and IFN-γ levels were exaggerated by CRSR. Data represent means ± SEM, n = 6; *P < 0.05, **P < 0.01, ***P < 0.0001.