title: Astrocytes accumulate 4-hydroxynonenal adducts in murine scrapie and human Creutzfeldt-Jakob disease.
abstract: Scrapie-infected mice are considered a model for study in prion diseases, which are characterized by the progressive accumulation in the brain of an abnormal isoform (PrPsc) of the normal cellular prion protein (PrPc). Increasing data suggest that the neurodegenerative process in prion diseases may result, at least partially, from a defect in antioxidant function, but so far in vivo oxidative stress remains poorly documented. We report here that 4-hydroxynonenal, a lipid peroxidation by-product, forms protein adducts in brains of scrapie-infected mice and of Creutzfeldt-Jakob disease affected patients. In scrapie mice, studies on the progression of PrPsc accumulation, glial activation, ubiquitin deposition, and 4-HNE adduct formation allowed us to conclude the late occurrence of oxidative damage in the course of the disease. Massive 4-HNE accumulation was identified in astrocytes, but not in neurons or microglial cells. These findings suggest an important oxidative stress (and subsequent lipid peroxidation) in astrocytes, with possible consequences on their neuronal trophic function.
authors.affiliation: UMR INRA-ENVT, Physiopathologie Infectieuse et Parasitaire des Ruminants, Ecole Nationale Vétérinaire de Toulouse, 31076, Toulouse, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Andreoletti
authors.forename: Etienne
authors.initials: E
authors.lastname: Levavasseur
authors.forename: Emmanuelle
authors.initials: E
authors.lastname: Uro-Coste
authors.forename: Guillaume
authors.initials: G
authors.lastname: Tabouret
authors.forename: Pierre
authors.initials: P
authors.lastname: Sarradin
authors.forename: Marie-Bernadette
authors.initials: MB
authors.lastname: Delisle
authors.forename: Patricia
authors.initials: P
authors.lastname: Berthon
authors.forename: Robert
authors.initials: R
authors.lastname: Salvayre
authors.forename: François
authors.initials: F
authors.lastname: Schelcher
authors.forename: Anne
authors.initials: A
authors.lastname: Negre-Salvayre
mesh_terms: D000447:Aldehydes / Q000378:metabolism*; D000818:Animals; D001253:Astrocytes / Q000378:metabolism*; D001921:Brain / Q000378:metabolism*; D007562:Creutzfeldt-Jakob Syndrome / Q000378:metabolism*; D003432:Cross-Linking Reagents / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D015227:Lipid Peroxidation; D051379:Mice; D008810:Mice, Inbred C57BL; D017628:Microglia / Q000378:metabolism; D009474:Neurons / Q000378:metabolism; D018384:Oxidative Stress; D018620:PrPSc Proteins / Q000378:metabolism; D017096:Prion Diseases / Q000378:metabolism; D011328:Prions / Q000378:metabolism; D012608:Scrapie / Q000378:metabolism*; D025801:Ubiquitin / Q000378:metabolism
chemical_list: D000447:Aldehydes; D003432:Cross-Linking Reagents; D018620:PrPSc Proteins; D011328:Prions; D025801:Ubiquitin; C027576:4-hydroxy-2-nonenal