Abstract
Brain-derived neurotrophic factor (BDNF) is essential for cognitive and memory functions. Abnormal BDNF expression in the central nervous system may impair these functions. Anaesthesia and surgery can induce perioperative neurocognitive disorders (PND). Clinical studies show that BDNF expression is decreased in patients presenting with cognitive impairment after anaesthesia and surgery. However, the molecular mechanism is still unclear. Epigenetic regulation plays an important role in cognition. The hypermethylation of H3K9 is crucial for transcriptional silencing and the onset of cognitive disorders. Here, we hypothesised that H3K9 trimethylation repressed BDNF expression and impaired memory formation or recall during anaesthesia and surgery. Laparotomy under isoflurane inhalation anaesthesia, behavioural tests, Western blotting, quantitative real-time reverse-transcription polymerase chain reaction (qRT-PCR), chromatin immunoprecipitation (ChIP), and immunohistochemistry were used in this study. BDNF expression was decreased in the hippocampus after anaesthesia and surgery. Cognitive impairment affected memory formation but not recall. The trimethylation of H3K9 downregulated BDNF expression. The overexpression of BDNF or use of exogenous BDNF improved the impairment of memory formation caused by anaesthesia and surgery. Therefore, inhibiting H3K9 trimethylation and increasing the expression of BDNF may help prevent PND in the clinical setting.
Highlights
Postoperative cognitive changes are a common complication, especially in elderly patients who undergo major surgeries, including arthroplasty, laparotomy, and thoracotomy with or without cardiopulmonary bypass (Saczynski et al, 2012; Evered et al, 2018)
We assessed whether anaesthesia and surgery could downregulate Brainderived neurotrophic factor (BDNF) in the hippocampal dorsal CA1 area and whether laparotomy under inhalation anaesthesia in middle-aged mice was a well-established postoperative cognitive impairment model
We demonstrated that anaesthesia and surgery impaired cognition by repressing the expression of the Bdnf gene in the dorsal hippocampus, resulting in impairment of memory formation
Summary
Postoperative cognitive changes are a common complication, especially in elderly patients who undergo major surgeries, including arthroplasty, laparotomy, and thoracotomy with or without cardiopulmonary bypass (Saczynski et al, 2012; Evered et al, 2018). Perioperative neurocognitive disorders (PND) are characterised by symptoms such as disturbance of memory, attention, consciousness, information processing, and the sleep-wake cycle, leading to postoperative morbidity and mortality (Evered et al, 2018). Memory impairment after anaesthesia and surgery is a typical symptom and is often used as the main diagnostic criterion for PND (Evered et al, 2018). A clinical study reported that BDNF protein expression decreased after anaesthesia and surgery in patients with cognitive impairment (Wyrobek et al, 2017)
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