Characterization of DNA hydroxymethylation in the hypothalamus of elderly mice with post-operative cognitive dysfunction

Exp Ther Med. 2019 Nov;18(5):4002-4010. doi: 10.3892/etm.2019.8056. Epub 2019 Sep 26.

Abstract

Post-operative cognitive dysfunction (POCD) is a common syndrome characterized by perioperative cerebral damage in elderly patients, including cognitive impairment and memory loss. Recent studies have revealed that anesthesia is one of the key causes of POCD. 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, a POCD model was established in elderly mice through sevoflurane treatment, and these mice were found to have compromised levels of global DNA 5'-hydroxymethylcytosine (5hmC) and Uhrf2 in the hippocampus and the amygdaloid nucleus, when compared with non-POCD and control mice. The results of immunoprecipitation and quantitative PCR revealed that 5hmC modification of the promoters of genes associated with neural protection and development, such as glial cell-derived neurotrophic factor, brain derived neurotrophic factor, glucocorticoid receptor and acyl-CoA sythetase short chain family member 2, was reduced in the hippocampus of POCD mice when compared with non-POCD and control mice. Taken together, the findings of the present study suggest that loss of 5hmC, in the hippocampus and the amygdaloid nucleus modulated by Uhrf2 suppression, may result in the learning and memory ability impairment seen in mice with POCD.

Keywords: 5′-hydroxymethylcytosine; post-operative cognitive dysfunction; sevoflurane; ubiquitin-like with PHD and ring finger domains 2.