ArticleCNS neuroscience & therapeutics2023
A decrease in NR2B expression mediated by DNA hypermethylation induces perioperative neurocognitive disorder in aged mice.
Article in CNS neuroscience & therapeutics, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 27 citations in OpenAlex.
- Epigenetic Mechanisms in Perioperative Medicine: From Neuroinflammation and NETosis to Organ Dysfunction and Precision Therapeutics.Biomedicines · 2026Review
- FADS1 contributes to anesthesia/surgery-induced cognitive impairment by aggravating omega-6 fatty acid metabolic disruption in aged mice.Journal of neuroinflammation · 2026Article
- Inhibiting Liver-Derived C3 Protein Rescues Anesthesia/Surgery-Induced Cognitive Impairment, Synaptic Disorders, and Microglial Phagocytosis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Perioperative neurocognitive disorders: Advances in molecular mechanisms and bioactive molecules.Ageing research reviews · 2025Review
- GABAAnnals of medicine · 2025Article
- Tat-NR2B9c prevent cognitive dysfunction in mice modeling Alzheimer's Disease induced by AβIBRO neuroscience reports · 2025Article
- DNMT3a Deficiency Contributes to Anesthesia/Surgery-Induced Synaptic Dysfunction and Cognitive Impairment in Aged Mice.Aging cell · 2025Article
- Structural basis for the inhibition of cystathionine-β-synthase by isoflurane and its role in anaesthesia-induced social dysfunction in mice.British journal of anaesthesia · 2025Article
- Effect of remote ischemic preconditioning on perioperative neurocognitive disorder in elderly patients undergoing major surgery and associated genetic variant analysis: a randomized clinical trial.Perioperative medicine (London, England) · 2025Article
- Hypoxic Postconditioning Offers Neuroprotection Against Transient Cerebral Ischemia via Down-Regulation of rno_piR_011022.CNS neuroscience & therapeutics · 2025Article
- Integration of Methylation and Gene Expression Deciphered Candidate Biomarkers DAB2IP and SMYD3 in Delayed Encephalopathy After Carbon Monoxide Poisoning.CNS neuroscience & therapeutics · 2025Article
- Connexin 43 contributes to perioperative neurocognitive disorder by attenuating perineuronal net of hippocampus in aged mice.Cellular and molecular life sciences : CMLS · 2025Article
- Association between GRIN2B DNA methylation and cognitive impairment: a cross-sectional study of patients with bipolar depression.Frontiers in psychiatry · 2025Article
- Inhibiting endoplasmic reticulum stress alleviates perioperative neurocognitive disorders by reducing neuroinflammation mediated by NLRP3 inflammasome activation.CNS neuroscience & therapeutics · 2024Article
- Neuronal-specific TNFAIP1 ablation attenuates postoperative cognitive dysfunction via targeting SNAP25 for K48-linked ubiquitination.Cell communication and signaling : CCS · 2023Article
- A decrease in NR2B expression mediated by DNA hypermethylation induces perioperative neurocognitive disorder in aged mice.CNS neuroscience & therapeutics · 2023Article
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
aimsThis study was designed to investigate the role of NR2B and the contribution of DNA methylation to NR2B expression in the pathogenesis of PND.
methodsEighteen-month-old C57BL/6J mice were subjected to experimental laparotomy under 1.4% isoflurane anesthesia. Hippocampus-dependent learning and memory were evaluated by using the Barnes maze and contextual fear conditioning tests. The protein and mRNA expression levels of NR2B were evaluated by western blotting and qRT-PCR respectively, and the methylation of the NR2B gene was examined by using targeted bisulfite sequencing. Long-term synaptic plasticity (LTP) was measured by electrophysiology.
resultsMice that underwent laparotomy exhibited hippocampus-dependent cognitive deficits accompanied by decreased NR2B expressions and LTP deficiency. The overexpression of NR2B in the dorsal hippocampus could improve learning and memory in mice subjected to laparotomy. In particular, the decreased NR2B expressions induced by laparotomy was attributed to the NR2B gene hypermethylation. Preoperative administration of S-adenosylmethionine (SAM) could hypomethylate the NR2B gene, upregulate NR2B expression and improve LTP, exerting a dose-dependent therapeutic effect against PND. Moreover, inhibiting NR2B abrogated the benefits of SAM pretreatment.
conclusionsLaparotomy cause hippocampus-dependent cognitive decline by hypermethylating the NR2B gene, allowing us to understand the pathogenesis of PND in an epigenetic landscape.
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