METHODS: Eight-week-old C57BL/6J male mice with or without EE for 3, 7, or 14 days had right carotid artery exposure under isoflurane anesthesia. An anti-neuroligin 1 antibody at 1.5 µg/mouse was injected intracerebroventricularly at one and two weeks before the surgery. Mice were subjected to the Barnes maze and fear conditioning tests from one week after the surgery. Cerebral cortex and hippocampus were harvested after surgery.
RESULTS: Mice with surgery had poorer performance in the Barnes maze and fear conditioning tests than control mice. EE for 2 weeks, but not EE for 3 or 7 days, improved the performance of surgery mice in these tests. Surgery reduced neuroligin 1 in the hippocampus. Preoperative EE for 2 weeks attenuated this reduction. The anti-neuroligin 1 antibody worsened the performance of mice with surgery plus EE in the Barnes maze and fear conditioning tests. Surgery increased histone deacetylase activity and decreased the acetylated histone in the hippocampus. EE attenuated these surgery effects.
CONCLUSIONS: Our results suggest that preoperative EE for 2 weeks reduces POCD. This effect may be mediated by preserving neuroligin 1 expression via attenuating surgery-induced epigenetic dysregulation in the brain.