Effect of preoperative sleep deprivation on hippocampal TLR4/NF-κB signaling pathway in aged mice with postoperative cognitive dysfunction

Abstract

Objective To evaluate the effect of preoperative sleep deprivation on hippocampal Toll-like receptor 4(TLR4)/nuclear factor-kappa B(NF-κB)signaling pathway in aged mice with postoperative cognitive dysfunction. Methods Sixty clean-grade healthy male C57BL/6J mice, aged 16 months, weighing 28-36 g, were divided into 4 groups(n=15 each)using a random number table method: control group(group C), surgery group(group S), sleep deprivation group(group SD)and sleep deprivation plus surgery group(group SD+ S). Mice were fed a common diet in group C. Mice were sleep-deprived for 24 h in group SD. Tibial fracture internal fixation was performed in group S. Tibial fracture internal fixation was performed after 24-h sleep deprivation in group SD+ S. Cognitive function was assessed using the contextual fear conditioning test at days 3 and 7 after operation. The animals were sacrificed at day 7 after operation, brains were removed and hippocampi were isolated for determination of tumor necrosis factor-alpha(TNF-α)content(by enzyme-linked immunosorbent assay)and expression of TLR4 and p-NF-κB p65(by Western blot). Results Compared with group C, the percentage of time spent freezing induced by condition and percentage of time spent freezing induced by context were significantly decreased at days 3 and 7 after operation, the content of TNF-α was increased, and the expression of TLR4 and p-NF-κB p65 was up-regulated in S, SD and SD+ S groups(P<0.05). Compared with group S and group SD, the percentage of time spent freezing induced by condition and percentage of time spent freezing induced by context were significantly decreased at days 3 and 7 after operation, the content of TNF-α was increased, and the expression of TLR4 and p-NF-κB p65 was up-regulated in group SD+ S(P<0.05). Conclusion Preoperative sleep deprivation further accentuates postoperative cognitive dysfunction, and the mechanism is related to activating TLR4/NF-κB signaling pathway and inducing inflammatory responses of aged mice. Key words: Sleep deprivation; Aged; Cognition disorders; Hippocampus; Toll-like receptors; NF-kappa B