Astrocytes accumulate 4-hydroxynonenal adducts in murine scrapie and human Creutzfeldt-Jakob disease.
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.
Andreoletti
Olivier
O
UMR INRA-ENVT, Physiopathologie Infectieuse et Parasitaire des Ruminants, Ecole Nationale Vétérinaire de Toulouse, 31076, Toulouse, France.
Levavasseur
Etienne
E
Uro-Coste
Emmanuelle
E
Tabouret
Guillaume
G
Sarradin
Pierre
P
Delisle
Marie-Bernadette
MB
Berthon
Patricia
P
Salvayre
Robert
R
Schelcher
François
F
Negre-Salvayre
Anne
A
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
D000447:Aldehydes; D003432:Cross-Linking Reagents; D018620:PrPSc Proteins; D011328:Prions; D025801:Ubiquitin; C027576:4-hydroxy-2-nonenal