Sleep Fragmentation Induces Activation of NOD-Like Receptor Protein-3 Inflammasome in Rat Hippocampus

Abstract

Background and Objective Continuous sleep is important for cognitive function; studies have shown that disrupted sleep has a deleterious effect on hippocampus-dependent cognitive function, but the exact mechanism is unknown. The inflammasome NOD-like receptor protein-3 (NLRP-3) has been reported to cause memory and cognitive dysfunction, but no studies have examined whether NLRP-3 is up-regulated in the hippocampus by sleep fragmentation (SF). Therefore, we investigated whether SF affected NLRP-3 activation in the rat hippocampus in a wheel-based SF model. Methods We randomly divided 7-week-old male Wistar rats into 4-day SF, 4-day exercise control (EC), 8-day SF, and 8-day EC groups. SF was accomplished with a forced walking wheel with a 30-s on/90-s off cycle, and we set EC at 10 min on/30 min off. We performed Western blots to compare NLRP-3 expression levels, and we measured malondialdehyde (MDA) levels in the hippocampus with a commercial kit. Results The SF group had more but shorter NREM bouts. Western blot analysis revealed that 4 and 8 days of SF up-regulated the expression of the NLRP-3 complex in the hippocampus including ASC, caspase-1, and IL-1β. Thioredoxin-interacting protein expression also increased more in the SF group, and the MDA level increases were greater in the SF groups than in the corresponding EC groups. Conclusions SF up-regulates NLRP-3 in the hippocampus. Additional behavioral and mechanistic studies are required to clarify the role of NLRP-3 in the hippocampi of rats subjected to SF.

Keywords

• Sleep fragmentation
• NLRP-3
• Hippocampus
• Malondialdehyde