High-fat diet aggravates postoperative cognitive dysfunction in aged mice.

BACKGROUND: Silent Information Regulator 1 (Sirt1) and apoptosis play key roles in postoperative cognitive dysfunction (POCD). Consuming a high-fat diet (HFD), a prevalent type of diet in modern society, has been increasingly recognized as contributing to neurodegenerative diseases. Although Sirt1 and apoptosis are significant responders to HFD in the brain, little is known regarding the functional correlations between HFD and POCD.

METHODS: Thirty-two aged C57BL/6 male mice were randomly divided into 2 groups: an ad libitum (AL) group (fed a regular diet) and high-fat diet (HF) group (fed a high-fat diet). After 8 weeks, the animals were divided into four sub-groups: an ad libitum control (ALC) group, ad libitum surgery (ALS) group, high-fat diet control (HFC) group, and high-fat diet surgery (HFS) group. The ALS and HFS groups were exposed to 3% sevoflurane in 33% oxygen for 3 h and were subsequently subjected to exploratory surgery to establish the POCD model. The ALC and HFC groups were treated with 33% oxygen for 3 h without surgery. After 48 h, the learning and memory abilities of mice in each group were tested using the Morris water maze (MWM). The expression levels of Sirt1, Bcl-2, Bax and caspase-3 cleaved were detected by western blot.

RESULTS: The MWM and western blotting results showed that the learning and memory abilities were decreased in the HFC group compared with the ALC group. The learning and memory abilities and the expression of Sirt1 in the hippocampus in the HFS group were significantly decreased compared with the other groups. A significant decrease in Sirt1 expression was also observed in the HFC group compared with the ALS group. The level of Bcl-2 was lower in the HFS group than in the HFC and ALC groups. The expression levels of caspase-3 cleaved and Bax increased in the HFS group compared with the HFC group. Moreover, the expression of caspase-3 cleaved was higher in the HFC group than in the ALS group.

CONCLUSION: HFD can aggravate POCD in aged C57BL/6 mice, an effect that may be related to the inhibition expression of Sirt1 and the promotion of neuronal apoptosis.