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Updated: Apr 21, 2026
A Mouse Model of Orthopedic Surgery to Study Postoperative Cognitive Dysfunction and Tissue Regeneration
Published on: February 27, 2018
Microglial PGC-1α alleviates synaptic damage and cognitive impairments following anesthesia and surgery by
Xuyang Wu1, Maokai Xu1, Yongxin Huang1
1Department of Anesthesiology, Shengli Clinical Medical College of Fujian Medical University, Fujian Provincial Hospital, Fuzhou University Affiliated Provincial Hospital, Fuzhou, China.
Abstract:
Postoperative cognitive dysfunction (POCD) in the elderly is a serious clinical concern. Although microglial phagocytosis is known to depend on mitochondrial metabolism, and its dysregulation can lead to abnormal synaptic pruning and neuronal injury, the molecular link between these processes in POCD pathogenesis requires further elucidation. In this study, we established a POCD animal model of aged mice using isoflurane exposure and partial hepatectomy to investigate how anesthesia and surgery impacted synaptic plasticity via microglial phagocytosis. Our findings demonstrated that anesthesia and surgery significantly reduced hippocampal peroxisome proliferators-activated receptor γ coactivator-1α (PGC-1α) expression, leading to impaired mitochondrial energy metabolism, abnormal microglial phagocytosis and excessive synaptic pruning, which was associated with synaptic deficits and cognitive dysfunction. Importantly, the treatment with the PGC-1α activator ZLN005 or AAV-mediated overexpression of PGC-1α not only successfully restored PGC-1α level in the hippocampus of aged mice, but also effectively ameliorated mitochondrial dysfunction, reversed abnormal microglia-mediated synaptic pruning, restored synaptic plasticity, and improved POCD. Our findings identify microglial PGC-1α as a critical mediator in the pathogenesis of POCD, linking mitochondrial energy metabolism with microglia-mediated synaptic pruning, and highlight the potential of microglial PGC-1α as a promising therapeutic target for prevention and treatment of POCD.
Insights
Anesthesia and surgery impair brain function in elderly mice by disrupting microglial energy metabolism, leading to cognitive decline. Restoring peroxisome proliferators-activated receptor γ coactivator-1α (PGC-1α) in microglia prevents this dysfunction.
Area of Science:
- Neuroscience
- Mitochondrial Biology
- Immunology
Background:
- Postoperative cognitive dysfunction (POCD) is a significant concern in the elderly.
- Microglial function, crucial for synaptic health, is linked to mitochondrial metabolism.
- The precise molecular mechanisms connecting mitochondrial dysfunction, microglial activity, and POCD remain unclear.
Purpose of the Study:
- To investigate the impact of anesthesia and surgery on synaptic plasticity in aged mice.
- To elucidate the role of microglial phagocytosis and mitochondrial metabolism in POCD pathogenesis.
- To identify potential therapeutic targets for preventing and treating POCD.
Main Methods:
- Established a POCD mouse model using isoflurane anesthesia and partial hepatectomy in aged mice.
- Assessed hippocampal peroxisome proliferators-activated receptor γ coactivator-1α (PGC-1α) expression, mitochondrial function, and microglial phagocytosis.
- Administered PGC-1α activator (ZLN005) or AAV-mediated PGC-1α overexpression to treated mice.
Main Results:
- Anesthesia and surgery reduced hippocampal PGC-1α, impairing mitochondrial metabolism, microglial phagocytosis, and synaptic plasticity, leading to cognitive deficits.
- PGC-1α activation or overexpression restored PGC-1α levels, ameliorated mitochondrial dysfunction, and reversed abnormal microglial pruning.
- Restored synaptic plasticity and cognitive function were observed in treated mice.
Conclusions:
- Microglial PGC-1α is a key mediator in POCD, linking mitochondrial energy metabolism to microglia-mediated synaptic pruning.
- Targeting microglial PGC-1α offers a promising therapeutic strategy for POCD.
- Findings highlight the critical role of mitochondrial health in maintaining cognitive function post-surgery.
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