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Original Research ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Mol. Neurosci. | doi: 10.3389/fnmol.2019.00246

Trimethylation of histone H3K9 inducing brain-derived neurotrophy factor repression in dorsal hippocampus impaired memory acquisition during anesthesia and surgery

 Tong Wu1, 2,  Xiao-Yu Sun1,  Xiu Yang1,  Le Liu1,  Kun Tong1, Ya Gao1, Jing-Ru Hao1, Jing Cao3 and  Can Gao1*
  • 1Xuzhou Medical University, China
  • 2Affiliated Hospital of Xuzhou Medical University, China
  • 3Xuzhou Central Hospital, China

The BDNF is essential in cognition and memory. Abnormal BDNF expression in central nerve system may result in cognition and memory attenuation. Anesthesia and surgery may induce perioperative neurocognitive disorders (PND). Clinical studies show that the BDNF expression is decreased in patients suffering the cognitive impairment after anesthesia and surgery. However, the neuropathogenesis remains largely unknown. The epigenetic regulation plays an important role in cognition. Hypermethylation of H3K9 is relevant to transcriptional silence and cognitive disorder. Here, we hypothesized that the H3K9 trimethylation repressed BDNF expression and impaired memory formation or recall during anesthesia and surgery. Laparotomy under isoflurane inhalation anesthesia model, various behavioral tests, western blotting, quantitative real-time reverse transcription polymerase chain reaction, chromatin immunoprecipitation and immunohistochemistry were used in this study. We found that the BDNF expression was decreased in hippocampus after anesthesia and surgery. The cognition impairment affected memory acquisition instead of recall. Trimethylation of H3K9 induced the repression of BDNF. Overexpression of BDNF or complement of exogenous BDNF rescued the acquisition of memory after anesthesia and surgery. Inhibiting H3K9 trimethylation and improving the expression of BDNF could avoid PND for clinical applications.

Keywords: anesthesia and surgery, H3K9, trimethylation, Brain-derived neurotrophy factor, Hippocampus, memory acquisition

Received: 09 Jul 2019; Accepted: 24 Sep 2019.

Copyright: © 2019 Wu, Sun, Yang, Liu, Tong, Gao, Hao, Cao and Gao. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: MD, PhD. Can Gao, Xuzhou Medical University, Xuzhou, China, gaocan@xzhmu.edu.cn