Sevoflurane aggravates cognitive impairment in OSAS mice through tau phosphorylation and mitochondrial dysfunction.

Abstract

With an aging population, the incidence of obstructive sleep apnea syndrome (OSAS) is rising, resulting in a growing number of patients undergoing surgery who are also affected by OSAS. The combined impact of anesthetic drugs and OSAS-related neurological damage has drawn significant attention. Here, wild-type (WT) and Tau-knockout (Tau-KO) mice were subjected to intermittent hypoxia and sevoflurane exposure to induce OSAS and sevoflurane-induced neurotoxicity. Protein expression of tau phosphorylation (Tau-Ser202/Thr205 and Tau-Ser422) was measured by Western blotting. Immunofluorescence was used to visualize tau phosphorylation (Tau-Ser202/Thr205) in the hippocampal CA1 region. Mitochondrial function was evaluated by measuring reactive oxygen species (ROS), mitochondrial membrane potential (MMP), and ATP levels. Cognitive functions were assessed using the Morris water maze and Y-maze tests. We found that compared to the WT OSAS group, sevoflurane significantly increased tau phosphorylation and mitochondrial dysfunction in WT OSAS mice, leading to cognitive impairment. Interestingly, idebenone treatment mitigated sevoflurane-induced mitochondrial dysfunction and cognitive impairment in WT OSAS mice, but it did not affect tau phosphorylation. Compared to the Tau-KO control group, Tau-KO OSAS mice exhibited mitochondrial dysfunction and cognitive impairment, but sevoflurane did not exacerbate mitochondrial dysfunction or cognitive impairment in these mice. These findings suggest that sevoflurane exacerbates cognitive impairments in OSAS mice through tau phosphorylation-induced mitochondrial dysfunction, but also uncovered differing mechanisms between cognitive impairments induced by OSAS and those exacerbated by sevoflurane.