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Updated: Nov 21, 2025
A Mouse Model of Orthopedic Surgery to Study Postoperative Cognitive Dysfunction and Tissue Regeneration
Published on: February 27, 2018
Surgery-induced downregulation of hippocampal sirtuin-1 contributes to cognitive dysfunction by inhibiting autophagy
Qian-Juan Fang1,2, Bing-Huan Chi1,2, Qi-Cheng Lin1,2
1Department of Anesthesiology and Perioperative Medicine, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University Wenzhou 325027, Zhejiang, China.
Objectives:
Elderly patients often suffer from cognitive dysfunction following surgery. However, the mechanisms underlying this phenomenon still remain unclear. This study investigated the critical part of Sirtuin-1 (SIRT1)-mediated autophagy and apoptosis in surgery-induced cognitive impairment.
Methods:
The aged (16-month-old) male C57BL/6 mice underwent anesthesia and surgery. Some mice received intraperitoneal injections of resveratrol, which is an activator of SIRT1, prior to exposure to splenectomy. To examine learning and memory behavior in different sets, the study performed a Morris water maze. Tissues from the hippocampus were harvested 1, 3 and 7 days after surgery. Western blotting and immunofluorescence analysis determined the expression of autophagy- and apoptosis- associated protein.
Results:
This article demonstrated surgery but not anesthesia considerably affected memory behavior and downregulated SIRT1 expression in the aged mice. Interestingly, rescue of hippocampal SIRT1 expression ameliorated the cognitive impairment in the elderly mice under splenectomy. In addition, surgical trauma decreased Beclin-1 protein levels and the LC3-II/LC3-I ratio, while expression of p62, Bax and cleaved caspase-3 in hippocampal neurons increased. However, rescue of hippocampal SIRT1 expression considerably attenuated the surgery-induced downregulation of Beclin-1, increased the ratio of LC3-II/LC3-I, and decreased expression of p62, Bax, and cleaved caspase-3.
Conclusion:
These findings suggest that surgery-induced downregulation of hippocampal SIRT1 participates in cognitive impairment after surgery by inhibiting the autophagy process and activating apoptosis.
Insights
Surgery impairs memory in elderly mice by reducing Sirtuin-1 (SIRT1), which inhibits autophagy and promotes apoptosis in the hippocampus. Restoring SIRT1 levels improved cognitive function.
Area of Science:
- Neuroscience
- Gerontology
- Molecular Biology
Background:
- Post-surgical cognitive dysfunction is a significant concern in elderly patients.
- The underlying molecular mechanisms, particularly involving Sirtuin-1 (SIRT1), autophagy, and apoptosis, remain incompletely understood.
Purpose of the Study:
- To investigate the role of SIRT1-mediated autophagy and apoptosis in surgery-induced cognitive impairment in aged mice.
Main Methods:
- Aged mice underwent splenectomy surgery; some received resveratrol to activate SIRT1.
- Learning and memory were assessed using the Morris water maze.
- Hippocampal tissues were analyzed for autophagy and apoptosis-related proteins via Western blotting and immunofluorescence.
Main Results:
- Surgery, not anesthesia, impaired memory and reduced hippocampal SIRT1 expression.
- Restoring SIRT1 ameliorated cognitive deficits.
- Surgery decreased autophagy markers (Beclin-1, LC3-II/LC3-I ratio) and increased apoptosis markers (p62, Bax, cleaved caspase-3).
- SIRT1 restoration reversed these changes.
Conclusions:
- Surgery-induced cognitive impairment in aged mice is linked to SIRT1 downregulation.
- This downregulation inhibits autophagy and promotes apoptosis in the hippocampus.
