title: Sevoflurane alters the expression of receptors and enzymes involved in Aβ clearance in rats.
abstract: BACKGROUND
  Patients with Alzheimer's disease (AD) exhibit a failure in the clearance of amyloid β peptides (Aβ) from the central nervous system. Previous studies have suggested an association between anesthesia and the occurrence of AD. The aim of the present report was to further explore this possibility.
  
  
  METHODS
  Animals were administered sevoflurane for 2 h. We performed immunohistochemistry and real-time polymerase chain reaction to assess the levels of low-density lipoprotein receptor-related protein 1 (LRP-1), the receptor for advanced glycation end products (RAGE) protein, insulin-degrading enzyme (IDE), and neprilysin (NEP) in aged and young rat's brain.
  
  
  RESULTS
  Levels of LRP-1 were significantly decreased, while those of RAGE increased in the aged and young groups. Immunoreactivity for IDE was significantly decreased at 3 and increased at 15 days in the young group. In contrast, immunoreactivity for NEP was significantly increased at 1 but decreased at 15 days in aged rats. Levels of IDE messenger RNA (mRNA) were significantly decreased at 3 and 7 days in the aged group but was consistently decreased at 1, 3, 7, and 15 days in the young group. Levels of NEP mRNA were significantly decreased in the aged group but increased in the young group at 1, 3, 7, and 15 days.
  
  
  CONCLUSIONS
  Sevoflurane leads to a reduction in the levels of LRP-1, while increasing RAGE and decreasing IDE and NEP in both aged and, to a lesser extent, young rat's brain. These receptor and enzymatic changes may promote the accumulation of Aβ in brain tissues and thus exacerbate Alzheimer's-like pathology.
authors.affiliation: Department of Anesthesiology, Beijing Military General Hospital, Beijing, China. lyzgao@gmail.com
authors.forename: Y
authors.initials: Y
authors.lastname: Liu
authors.forename: M
authors.initials: M
authors.lastname: Gao
authors.forename: L
authors.initials: L
authors.lastname: Ma
authors.forename: L
authors.initials: L
authors.lastname: Zhang
authors.forename: N
authors.initials: N
authors.lastname: Pan
mesh_terms: D000375:Aging / Q000378:metabolism; D000544:Alzheimer Disease / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D018685:Anesthetics, Inhalation / Q000633:toxicity*; D000818:Animals; D001812:Blood-Brain Barrier / Q000187:drug effects; D001921:Brain / Q000201:enzymology; D001923:Brain Chemistry / Q000187:drug effects*; D056547:CA1 Region, Hippocampal / Q000737:chemistry / Q000187:drug effects / Q000201:enzymology; D005260:Female; D007339:Insulysin / Q000032:analysis / Q000096:biosynthesis / Q000235:genetics; D026503:Low Density Lipoprotein Receptor-Related Protein-1 / Q000032:analysis / Q000096:biosynthesis / Q000235:genetics; D008738:Methyl Ethers / Q000633:toxicity*; D015260:Neprilysin / Q000032:analysis / Q000096:biosynthesis / Q000235:genetics; D009419:Nerve Tissue Proteins / Q000032:analysis* / Q000096:biosynthesis / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D060888:Real-Time Polymerase Chain Reaction; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000032:analysis / Q000096:biosynthesis / Q000235:genetics; D000077149:Sevoflurane; D013997:Time Factors
chemical_list: D016229:Amyloid beta-Peptides; D018685:Anesthetics, Inhalation; D026503:Low Density Lipoprotein Receptor-Related Protein-1; D008738:Methyl Ethers; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic; D000077149:Sevoflurane; D015260:Neprilysin; D007339:Insulysin