Decreased PSD95 expression in medial prefrontal cortex (mPFC) was associated with cognitive impairment induced by sevoflurane anesthesia.

Abstract

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.

• Authors: Yun-zhi Ling, Wei Ma, Li Yu, Ye Zhang, Qi-sheng Liang
• Journal: Journal of Zhejiang University. Science. B (J Zhejiang Univ Sci B) Vol. 16 Issue 9 Pg. 763-71 (Sep 2015) ISSN: 1862-1783 [Electronic] China
• PMID: 26365118 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Anesthetics, Inhalation
• Disks Large Homolog 4 Protein
• Dlg4 protein, rat
• Intracellular Signaling Peptides and Proteins
• Membrane Proteins
• Methyl Ethers
• Sevoflurane

Topics

• Anesthetics, Inhalation (adverse effects)
• Animals
• Cognition Disorders (chemically induced, metabolism)
• Disks Large Homolog 4 Protein
• Dose-Response Relationship, Drug
• Down-Regulation (drug effects)
• Intracellular Signaling Peptides and Proteins (metabolism)
• Male
• Membrane Proteins (metabolism)
• Memory, Short-Term (drug effects)
• Methyl Ethers (adverse effects)
• Prefrontal Cortex (drug effects, metabolism)
• Rats
• Rats, Wistar
• Sevoflurane