Characterization of DNA hydroxymethylation in hypothalamus of elderly mice with postoperative cognitive dysfunction

Abstract

Postoperative cognitive dysfunction (POCD) is a common syndrome with perioperative cerebral damage in elderly patients, displaying cognitive impairment and memory loss. Current studies revealed that anesthesia is one of the important causes for POCD occurrence. Recently, Ubiquitin-like with PHD and Ring Finger Domains 2 (Uhrf2) has been reported to play a crucial role in regulating DNA methylation and hydroxymethylation, which are closely connected with memory building and erasure. However, whether narcotic drugs can affect Uhrf2 to impact on DNA methylation and hydroxymethylation in POCD is poorly understood. In this study, we established the elderly POCD mouse model through sevoflurane treatment, and observed the compromised levels of global DNA hydroxymethylated cytosine (5hmC) and Uhrf2 in hippocampus and amygdaloid nucleus compared to non-POCD and control. Furthermore, 5hmC modification on the promoters of the genes associated with neural protection and development, such as GDNF, BDNF, GCR, ACSS2 were reduced in the hippocampus of POCD compared to non-POCD and control groups by MedIP qPCR. Taken together, our findings determined that the loss of 5hmC in hippocampus and amygdaloid nucleus modulated by Uhrf2 suppression might result in the learning and memory ability impairment in POCD.