Fatal neurological disease in scrapie-infected mice induced for experimental autoimmune encephalomyelitis

Yael Friedman-Levi, Haim Ovadia, Romana Hoftberger, Ofira Einstein, Oded Abramsky, Herbert Budka, Ruth Gabizon

Research output: Contribution to journalArticlepeer-review

15 Scopus citations


During the years or decades of prion disease incubation, at-risk individuals are certain to encounter diverse pathological insults, such as viral and bacterial infections, autoimmune diseases, or inflammatory processes. Whether prion disease incubation time and clinical signs or otherwise the pathology of intercurrent diseases can be affected by the coinfection process is unknown. To investigate this possibility, mice infected with the scrapie agent at both high and low titers were subsequently induced for experimental autoimmune encephalomyelitis, an immune system-mediated model of central nervous system (CNS) inflammation. We show here that coinduced mice died from a progressive neurological disease long before control mice succumbed to classical scrapie. To investigate the mechanism of the coinduced syndrome, we evaluated biochemical and pathological markers of both diseases. Brain and spleen PrP Sc levels in the dying coinduced mice were comparable to those observed in asymptomatic scrapie-infected animals, suggesting that coinduced disease is not an accelerated form of scrapie. In contrast, inflammatory markers, such as demyelination, immune cell infiltrates, and gliosis, were markedly increased in coinduced mouse spinal cords. Activated astrocytes were especially elevated in the medulla oblongata. Furthermore, PrPsc depositions were found in demyelinated white matter areas in coinduced mouse spinal cords, suggesting the presence of activated infected immune cells that infiltrate into the CNS to facilitate the process of prion neuroinvasion. We hypothesize that inflammatory processes affecting the CNS may have severe clinical implications in subjects incubating prion diseases.

Original languageEnglish
Pages (from-to)9942-9949
Number of pages8
JournalJournal of Virology
Issue number18
StatePublished - Sep 2007
Externally publishedYes


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