title: 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.affiliation: Department of Anesthesiology, the Second Affiliated Hospital of Anhui Medical University, Anhui 230601, China.|Department of Anesthesiology, the First Affiliated Hospital of Bengbu Medical College, Anhui 233004, China.
authors.forename: Yun-zhi
authors.initials: YZ
authors.lastname: Ling
authors.affiliation: Department of Preventive Treatment of Disease, Yulin City Hospital of Traditional Chinese Medicine, Shanxi 719000, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Ma
authors.affiliation: Department of Laboratory Medicine, Bengbu Medical College, Anhui 233003, China.
authors.forename: Li
authors.initials: L
authors.lastname: Yu
authors.affiliation: Department of Anesthesiology, the Second Affiliated Hospital of Anhui Medical University, Anhui 230601, China.
authors.forename: Ye
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Anesthesiology, the First Affiliated Hospital of Bengbu Medical College, Anhui 233004, China.
authors.forename: Qi-sheng
authors.initials: QS
authors.lastname: Liang
mesh_terms: D018685:Anesthetics, Inhalation / Q000009:adverse effects; D000818:Animals; D003072:Cognition Disorders / Q000139:chemically induced* / Q000378:metabolism*; D000076122:Disks Large Homolog 4 Protein; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation / Q000187:drug effects; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism*; D008570:Memory, Short-Term / Q000187:drug effects; D008738:Methyl Ethers / Q000009:adverse effects*; D017397:Prefrontal Cortex / Q000187:drug effects* / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D000077149:Sevoflurane
chemical_list: D018685:Anesthetics, Inhalation; D000076122:Disks Large Homolog 4 Protein; C501449:Dlg4 protein, rat; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D008738:Methyl Ethers; D000077149:Sevoflurane
keywords: Cognitive dysfunction; PSD95; Sevoflurane