Sevoflurane Inhibits Histone Acetylation and Contributes to Cognitive Dysfunction by Enhancing the Expression of ANP32A in Aged Mice

Postoperative cognitive dysfunction (POCD) is a major clinical complication after surgery under general anesthesia, especially in elderly patients. However, the mechanisms are still unclear. Recently, we found that the anaesthetization of aged C57BL/6J mice (14-16 months) with sevoflurane (3%, two hours each day for three consecutive days) can induce cognitive dysfunction, as well as synaptic plasticity deficits. Further studies demonstrated that sevoflurane induced ANP32A (Acidic leucine-rich nuclear phosphoprotein-32A) overexpression by stimulating C/EBPβ (CCAAT/enhancer binding protein-β), which could suppress histone acetylation at H3K18, H3K14, H4K5, and H4K12, and decrease the binding of H3K18 and H3K14 to the promoter of GluN2B and GluN2A, respectively. These results suggest that sevoflurane can inhibit histone acetylation and contribute to cognitive dysfunction by enhancing the expression of ANP32A in aged mice. Our study provides new insights into aged-associated POCD and potential molecular markers for protection.