NR AWFC
AU Friedman-Levi,Y.; Ovadia,H.; Einstein,O.; Abramsky,O.; Gabizon,R.
TI Early death of scrapie infected mice after induction with EAE
QU International Conference - Prion 2006: Strategies, advances and trends towards protection of society - 3.10.-6.10.2006, Torino, Italy, Lingotto Conference Centre - Poster sessions PA-17
PT Konferenz-Poster
AB During the years or decades of prion disease incubation period, the at-risk individuals are certain to encounter diverse pathological insults, such as viral and bacterial infections and other inflammatory processes. Whether prion disease incubation time, location and accumulation of PrPsc or otherwise the pathological profile of prions and other diseases are affected by the co-infection process is unknown. Experimental autoimmune encephalomyelitis (EAE) is an immune-mediated disease of the CNS, used extensively as the animal model of multiple sclerosis (MS), as well as a model for brain inflammation. EAE in mice is induced by immunization with several myelin proteins resulting in an inflammatory response comprising of mononuclear cell infiltrates around venules, leading to demyelination, axonal pathology and gliosis. Damage to the brain and spinal cord is mediated by CD4+ Th1 cells and inflammatory cytokines. In this work, EAE was induced in C57BL/6 mice, that were previously infected with prions (i.c. or i.p.), by immunization with myelin oligodendrocyte glycoprotein (MOG) 35-55 peptide. Animals were observed daily for signs of EAE and scrapie or other neurological dysfunctions. EAE induction resulted in chronic paralysis of the tail and hind limbs. All control i.p. scrapie infected mice died after an incubation time of more than 200 days. Surprisingly, the co-infected animals died much earlier (90-181 days), following clinical signs combining scrapie infection and EAE. Similar results were obtained for i.c. inoculation of prions. Brain histological examination of the co-infected mice showed both immune cell infiltrates, as seen in EAE, and brain vacuoles, as seen in the scrapie controls. Western blot analysis did not show any detectable difference in the level of PrPc or PrPsc in the brains of the co-infected animals, when compared to animals incubating scrapie alone for the same period of time. Immunocytochemistry experiments to deduce changes in PrPsc location are in progress. We conclude that co-infection of prions and inflammatory insults can result in an early fatal neurological disease. Whether these results have implications regarding the vCJD epidemic remains to be established.
AD Department of Neurology, The Agnes Ginges Center for Human Neurogenetics, Hadassah University Hospital, Jerusalem Israel
SP englisch
PO Italien