J Bacteriol Virol.  2008 Mar;38(1):47-52. 10.4167/jbv.2008.38.1.47.

Increases in the Proteins Modified by Malondialdehyde and Hydroxynonenal in the Hippocampus of Prion-Infected Mice

• Kim JI
• Lee HG

• KMID: 2168518
• DOI: http://doi.org/10.4167/jbv.2008.38.1.47

Abstract

Prion diseases, also termed transmissible spongiform encephalopathies (TSEs), are rare and fatal neurodegenerative conditions that affect both humans and animals. Although there is increased evidence that oxidative stress plays an important role in the pathogenesis of these diseases, the direct relationship between an accumulation of abnormal prion protein (PrP(Sc)) and the occurrence of oxidative stress has not been studied. In the present study, we have investigated the cellular localization of proteins modified by lipid peroxidation end products and its correlation with PrP(Sc) accumulation in the brain of mice infected with the ME7 prion strain. Intense immunostaining of malondialdehyde (MDA)- and hydroxynonenal (HNE)-modified proteins were observed in the hippocampus of prion-infected mice. In serial section study, we found that these immunoreactivities were co-localized with glial fibrillary acidic protein (GFAP)-positive astrocytes as well as with PrP(Sc). These results clearly indicate that the heightened oxidative stress in the form of lipid peroxidation is closely associated with PrP(Sc) accumulation in astrocytes of prion-infected mice.

Keyword

Prion diseases; Oxidative stress; PrP(Sc); Lipid peroxidation end products; Astrocytes

MeSH Terms

Animals
Astrocytes
Brain
Glial Fibrillary Acidic Protein
Hippocampus
Humans
Lipid Peroxidation
Malondialdehyde
Mice
Oxidative Stress
Prion Diseases
Proteins
Sprains and Strains
Glial Fibrillary Acidic Protein
Malondialdehyde
Proteins

Figure

• 

  Figure 1. Immunohistochemical staining and cellular localizations of HNE- and MDA-modified proteins in the hippocampus of ME7 prion-infected mice. Brain sections from control (A & E) and ME7-infected mice (C & G) were immunostained with either anti-HNE-modified protein (A & C) or anti-MDA-modified protein antibody (E & F). Intense immunoreactivities of HNE- and MDA-modified proteins were observed in the infected group (C & G, respectively: arrows). Each serial section was also immunostained with anti-GFAP antibody (B, D, F & H) to examine the cellular localization of HNE- and MDA-modified proteins. HNE- and MDA-modified protein-positive cells were co-localized with GFAP-positive astrocytes (C vs. D, G vs. H, respectively: arrows). Each symbol (#, ##, ∗, ∗∗) indicates landmark blood vessel in adjacent section (A & B, C & D, E & F, G & H, respectively). ×400.

• 

  Figure 2. Co-localization of PrPSc with either HNE- or MDA-modified proteins in the hippocampus of ME7 prion-infected mice. Brain sections from ME7-infected mice were immunostained with either anti-HNE-modified protein (A), anti-MDA-modified protein (C), or anti-PrP antibody (B & D). Immunoreactivities of HNE-modified protein as well as MDA-modified protein were colocalized with PrPSc-positive astrocytes (A vs. B, C vs. D, respectively; arrows). Each symbol (∗, #) indicates landmark blood vessel in adjacent section (A & B, C & D, respectively). ×400.

Reference

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