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Research Article
Anshi Wu
Beijing Chao-Yang Hospital
Corresponding Author
ORCiD: https://orcid.org/0000-0003-2353-2184
License:
This work is licensed under a CC BY 4.0 License. Read Full License
Background
Postoperative cognitive dysfunction (POCD) is a debilitating neurological complication in surgical patients. Current studies mainly focus on microglia activation, however, less is known about the mechanism underlying neuronal synaptic changes involved in microglia activation. Recent studies indicate that silent information regulator 1 (SIRT1) plays critical roles in different neurological disorders, and is involved in microglia activation. Herein, we evaluated the effects of SIRT1 activation on POCD.
Methods
Exploratory laparotomy were employed on mice (12-14 month) under sevoflurane anesthesia to establish model of POCD. Transcriptional changes in hippocampus after anesthesia and surgery were evaluated by RNA sequencing. SIRT1 expression were verified by Western Blot. Mice were treated with SIRT1 agonist SRT1720 or vehicle after surgery. Changes in microglia morphology, microglial phagocytosis, as well as dystrophic neurites and dendritic spine density were determined. Cognitive functions were evaluated by Y maze and Morris water maze.
Results
SIRT1 expression levels were downregulated in anesthesia and surgery group. Anesthesia and surgery lead to microglia morphology alteration, enhanced synaptic engulfment, dendritic spine loss, and cognitive deficits in our mice model, all of which were alleviated by SRT1720 administration.
Conclusion
Our study unveils one of the roles of SIRT1 in POCD pathogenesis. SIRT1 activation may represent a therapeutic strategy for prevention and treatment of POCD.
Keywords
SIRT1, microglia, engulfment, postoperative cognitive dysfunction
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This is a preprint. It has not completed peer review.
Research Article
Anshi Wu
Beijing Chao-Yang Hospital
Corresponding Author
ORCiD: https://orcid.org/0000-0003-2353-2184
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
History
CURRENT STATUS: Posted
Version 1
Posted 18 Feb, 2021
No community comments so far
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
Subject Areas
Anesthesiology & Pain Medicine
License:
This work is licensed under a CC BY 4.0 License. Read Full License
Background
Postoperative cognitive dysfunction (POCD) is a debilitating neurological complication in surgical patients. Current studies mainly focus on microglia activation, however, less is known about the mechanism underlying neuronal synaptic changes involved in microglia activation. Recent studies indicate that silent information regulator 1 (SIRT1) plays critical roles in different neurological disorders, and is involved in microglia activation. Herein, we evaluated the effects of SIRT1 activation on POCD.
Methods
Exploratory laparotomy were employed on mice (12-14 month) under sevoflurane anesthesia to establish model of POCD. Transcriptional changes in hippocampus after anesthesia and surgery were evaluated by RNA sequencing. SIRT1 expression were verified by Western Blot. Mice were treated with SIRT1 agonist SRT1720 or vehicle after surgery. Changes in microglia morphology, microglial phagocytosis, as well as dystrophic neurites and dendritic spine density were determined. Cognitive functions were evaluated by Y maze and Morris water maze.
Results
SIRT1 expression levels were downregulated in anesthesia and surgery group. Anesthesia and surgery lead to microglia morphology alteration, enhanced synaptic engulfment, dendritic spine loss, and cognitive deficits in our mice model, all of which were alleviated by SRT1720 administration.
Conclusion
Our study unveils one of the roles of SIRT1 in POCD pathogenesis. SIRT1 activation may represent a therapeutic strategy for prevention and treatment of POCD.
Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6
Figure 7
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