Increased expression of osteopontin in the brain with scrapie infection.

The expression of osteopontin (OPN) was studied in the brains of mice with scrapie. Reverse transcriptase polymerase chain reaction (RT-PCR) and Western blot analysis showed that the expression of OPN protein and mRNA was increased significantly in the scrapie-infected brains compared to the controls. The increased expression of OPN protein was largely matched with the PrP(Sc) accumulation. Immunohistochemically, OPN was intensely immunostained in neurons of the midbrain at the time of scrapie infection initiation. Particularly, OPN immunostaining was noted in the reactive astrocytes and some microglia in the scrapie brains, while those cells were devoid of OPN immunoreactivity in control brains. Overall, these findings suggest that some neurons affected by PrP(Sc) at an early stage of scrapie transiently express OPN but subsequently succumb to cell death at a later stage of scrapie; astroglial cells after scrapie infection are activated to express OPN; and increased OPN expression in these cells may play an important role in the pathology of scrapie. The precise role of OPN in scrapie needs further study.