The pathological changes in peripheral organs of scrapie-infected animals

Abstract

Scrapie is an unconventional neurodegenerative disease in sheep and goats that has been known in Europe for over 260 Years. The scrapie agents affect the brain and are transmissible from animal to animal. Key features of scrapie infections are abnormal behavior and deficits in motor function. These clinical findings can be related to the damage found in the central nervous system. In some scrapie strain-host model systems there are other manifestations of disease that appear to be related to pathological changes found in the peripheral organs, especially in the endocrine organs such as pituitary, adrenal glands, the islet of Langerhans and ovary. In those model systems in which extensive histopathological changes have been seen in peripheral organs, the titers of scrapie infectivity and the levels of the scrapie specific protein, PrPSc, are relatively low in the affected organs. These data suggest but do not prove that changes in peripheral organs are secondary to the scrapie-induced neurodegeneration that is occurring in the brain. In some scrapie strain-host combinations, obesity and aberrant glucose metabolism are seen in the preclinical and clinical phases of the incubation period. There appear to be two pathways that lead to these particular clinical manifestations. In SJL mice infected by the ME7 or 22L strains of mouse-adapted scrapie and in some scrapie-infected sheep, the mechanism is related to changes induced in the hypothalamic-pituitary-adrenal axis. The other pathway is exemplified by hamsters infected with two hamster-adapted scrapie strains, 139H and 22CH; it appears that lesions found in the hypothalamic-islets of Langerhans axis are critical. A number of reviews on the pathological changes in the central nervous system have been published and therefore, in this review article, we focus on the gross and histopathological changes in peripheral organs in several scrapie strain-host combinations. The changes induced in peripheral organs in a number of scrapie strain-host combinations expand the number of diseases in which the unconventional slow infections could serve as a model. Further work in this area could help us to understand the mechanisms and pathways of the pathological changes found in the peripheral organs of the scrapie-infected animals.