Decreased PSD95 expression in medial prefrontal cortex (mPFC) was associated with cognitive impairment induced by
Yun-zhi Ling1,2, Wei Ma3, Li Yu4
1Department of Anesthesiology, the Second Affiliated Hospital of Anhui Medical University, Anhui 230601, China.
Objective:
Though sevoflurane has been widely used as an anesthetic in surgery, recent studies have shown that exposure to sevoflurane alone could lead to postoperative cognitive dysfunction (POCD), of which the mechanisms still remain largely unknown. The medial prefrontal cortex (mPFC) is known to be implicated in various cognitive impairments, including working memory and attentional processes. In the present study, we tried to identify dysregulated gene expression in mPFC and investigate the underlying mechanisms involved in POCD.
Methods:
Behavioral tests, including elevated plus-maze, O-maze, and Y-maze tests, were performed on Wistar rats exposed to sevoflurane. Whole-genome mRNA profiling of mPFC from Wistar rats after exposure to sevoflurane was carried out. Real-time polymerase chain reaction (PCR) was done to verify the differentially expressed genes.
Results:
Significant impairment of working memory of rats after exposure to sevoflurane was observed. A total of 119 of 7319 detected mRNAs showed significantly different expression between rats with and without sevoflurane exposure (fold change (FC)>2.0, P<0.05, and false discovery rate (FDR)<0.05), among which 74 mRNAs were down-regulated and 45 mRNAs were up-regulated. Postsynaptic density-95 (PSD95, also named DLG4) showed the most significantly decreased expression in mPFC and further investigation indicated that PSD95 expression level was correlated with spatial working memory performance.
Conclusions:
Our study revealed that PSD95 might be involved in the mechanism of POCD, which could provide clues for preventing POCD in clinical operations.
Insights
Sevoflurane anesthesia impairs working memory in rats. Gene expression analysis revealed decreased PSD95 in the medial prefrontal cortex, suggesting its role in postoperative cognitive dysfunction (POCD) mechanisms.
Area of Science:
- Neuroscience
- Anesthesiology
- Molecular Biology
Background:
- Sevoflurane is a common anesthetic.
- Sevoflurane exposure may cause postoperative cognitive dysfunction (POCD).
- Mechanisms of POCD are not fully understood, but the medial prefrontal cortex (mPFC) is implicated.
Purpose of the Study:
- Identify gene expression changes in the mPFC after sevoflurane exposure.
- Investigate molecular mechanisms underlying sevoflurane-induced POCD.
Main Methods:
- Wistar rats were exposed to sevoflurane.
- Behavioral tests (elevated plus-maze, O-maze, Y-maze) assessed cognitive function.
- Whole-genome mRNA profiling of mPFC was performed.
- Real-time PCR validated differentially expressed genes.
Main Results:
- Sevoflurane exposure significantly impaired working memory in rats.
- 119 mRNAs were differentially expressed in the mPFC (74 down-regulated, 45 up-regulated).
- Postsynaptic density-95 (PSD95) showed the most significant decrease and correlated with working memory performance.
Conclusions:
- Decreased PSD95 expression in the mPFC is implicated in sevoflurane-induced POCD.
- PSD95 may be a key factor in the mechanisms of POCD.
- Findings offer potential targets for preventing POCD in clinical settings.
