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Published on: January 30, 2014
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SIRT1 activation attenuates microglia-mediated synaptic engulfment in postoperative cognitive dysfunction
Yi Sun1, Yuzhu Wang1, Fan Ye2
1Department of Anesthesiology, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, China.
Frontiers in Aging Neuroscience
|November 28, 2022
Summary
Sirtuin-1 (SIRT1) activation may protect against postoperative cognitive dysfunction (POCD). This study found that SIRT1 levels decreased in a POCD mouse model, and its activation via SRT1720 improved cognitive deficits and synaptic changes.
Area of Science:
- Neuroscience
- Anesthesiology
- Gerontology
Background:
- Postoperative cognitive dysfunction (POCD) is a significant neurological complication following surgery.
- Research has primarily focused on microglial activation, with less understanding of neuronal synaptic changes.
- Sirtuin-1 (SIRT1) is implicated in neurological disorders through its role in microglial activation.
Purpose of the Study:
- To investigate the neuroprotective effects of Sirtuin-1 (SIRT1) activation in a mouse model of postoperative cognitive dysfunction (POCD).
- To explore the impact of SIRT1 on microglial activation and synaptic integrity in the context of POCD.
Main Methods:
- A mouse model of POCD was established using exploratory laparotomy under sevoflurane anesthesia.
- Hippocampal transcriptional changes were analyzed via RNA sequencing; SIRT1 expression was confirmed by Western Blot.
- Mice received the SIRT1 agonist SRT1720 or vehicle post-surgery, followed by assessments of microglia, neurites, dendritic spines, and cognitive function (Y maze, Morris water maze).
Main Results:
- SIRT1 expression was downregulated in the POCD model.
- Anesthesia and surgery induced microglial alterations, increased synaptic engulfment, dendritic spine loss, and cognitive impairments.
- SRT1720 administration mitigated these negative effects, improving cognitive performance and synaptic health.
Conclusions:
- SIRT1 plays a crucial neuroprotective role in the pathogenesis of POCD.
- Enhancing SIRT1 activity presents a potential therapeutic strategy for preventing and treating POCD.
