title: Propofol and thiopental suppress amyloid fibril formation and GM1 ganglioside expression through the γ-aminobutyric acid A receptor.
abstract: BACKGROUND
  The incidence of Alzheimer disease may increase after surgical interventions. Amyloid β-protein (Aβ) fibrillogenesis, which is closely related to Alzheimer disease, is reportedly accelerated by exposure to anesthetics. However, the effects of GM1 ganglioside (GM1) on Αβ fibrillogenesis have not yet been reported. The current study was designed to examine whether the anesthetics propofol and thiopental are associated with Αβ assembly and GM1 expression on the neuronal cell surface.
  
  
  METHODS
  PC12N cells and cultured neuronal cells were treated with propofol or thiopental, and GM1 expression in treated and untreated cells was determined by the specific binding of horseradish peroxidase-conjugated cholera toxin subunit B (n = 5). The effects of an inhibitor of the γ-aminobutyric acid A receptor was also examined (n= 5). In addition, the effects of the anesthetics on GM1 liposome-induced Αβ assembly were investigated (n = 5). Finally, the neurotoxicity of the assembled Αβ fibrils was studied by the lactate dehydrogenase release assay (n = 6).
  
  
  RESULTS
  Propofol (31.2 ± 4.7%) and thiopental (34.6 ± 10.5%) decreased GM1 expression on the cell surface through the γ-aminobutyric acid A receptor. The anesthetics inhibited Αβ fibril formation from soluble Αβ in cultured neurons. Moreover, propofol and thiopental suppressed GM1-induced fibril formation in a cell-free system (propofol, 75.8 ± 1.9%; thiopental, 83.6 ± 1.9%) and reduced the neurotoxicity of a mixture containing Aβ and GM1 liposomes (propofol, 35.3 ± 16.4%; thiopental, 21.3 ± 11.6%).
  
  
  CONCLUSIONS
  Propofol and thiopental have direct and indirect inhibitory effects on Αβ fibrillogenesis.
authors: Laboratory of Neurochemistry, Department of Pharmacy, College of Pharmaceutical Sciences, Ritsumeikan University, Kusatsu, Shiga, Japan. naokisan@ph.ritsumei.ac.jp
authors: Naoki
authors: N
authors: Yamamoto
authors: Hajime
authors: H
authors: Arima
authors: Takeshi
authors: T
authors: Sugiura
authors: Hiroyuki
authors: H
authors: Hirate
authors: Hideo
authors: H
authors: Taniura
authors: Kenji
authors: K
authors: Suzuki
authors: Kazuya
authors: K
authors: Sobue
mesh_terms: D000682:Amyloid / Q000187:drug effects*; D018686:Anesthetics, Intravenous / Q000494:pharmacology*; D000818:Animals; D002462:Cell Membrane / Q000187:drug effects; D002474:Cell-Free System; D002478:Cells, Cultured; D004195:Disease Models, Animal; D005677:G(M1) Ganglioside / Q000378:metabolism*; D008297:Male; D051379:Mice; D009474:Neurons / Q000187:drug effects; D016716:PC12 Cells; D015742:Propofol / Q000494:pharmacology*; D018079:Receptors, GABA / Q000378:metabolism*; D013874:Thiopental / Q000494:pharmacology*
chemical_list: D000682:Amyloid; D018686:Anesthetics, Intravenous; D018079:Receptors, GABA; D005677:G(M1) Ganglioside; D013874:Thiopental; D015742:Propofol