title: The 139H scrapie agent produces hypothalamic neurotoxicity and pancreatic islet histopathology: electron microscopic studies.
abstract: Neuronal degeneration, along with astrocytosis, spongiform vacuolation, and amyloid (PrPSc) formation, have long been regarded as neuropathological hallmarks of transmissible spongiform encephalopathies (TSEs). In animals, these diseases include; scrapie, transmissible mink encephalopathy, chronic wasting disease, bovine and feline spongiform encephalopathies, and in humans; kuru, Creutzfeldt-Jakob disease (CJD), and Gerstmann-Sträussler-Scheinker syndrome (GSS). The abnormal amyloid protein, (PrPSc) is toxic to neurons. Our previous studies showed that hamsters treated with 139H scrapie strain developed obesity, and generalized endocrinopathy, including lesions in hypothalamus, pituitary and pancreas. Histochemical and immunocytochemical studies revealed extensive pathological changes in the islets of Langerhans in 139H-infected hamsters, but not in hamsters infected with 263K scrapie strain. Using routine electron microscopy (EM), we have observed more details of lesions in the beta cells of islets of Langerhans in these animals. Cytoplasmic vacuolation occurred, cytoplasmic organelles were found damaged and disrupted, and membranes were occasionally ruptured. The width of endoplasmic reticulum (ER) lumina were 50-150 nm in controls, whereas in 139H-infected hamsters, they wee occasionally increased up to 4000 nm in diameter. Most beta cells showed degranulation. These EM observations suggest that the cellular death seen in the islets of Langerhans in 139H-infected hamsters is due to necrosis, not apoptosis. Since there were no amyloid deposits found in the islet of Langerhans at the EM level, and there were extremely low scrapie infectivity levels and PrPSc levels in pancreas, it is suggested that the changes noted in pancreas were not a direct toxic effect of PrPSc. Instead, our study suggests that scrapie prion protein PrPSc, acting as a neurotoxicant, alters the hypothalamic neuroendocrine regulation of the pancreas.
authors.affiliation: Division of Neurotoxicology, National Center for Toxicological Research, Jefferson, AR 72079, USA.
authors.forename: X
authors.initials: X
authors.lastname: Ye
authors.forename: A C
authors.initials: AC
authors.lastname: Scallet
authors.forename: R I
authors.initials: RI
authors.lastname: Carp
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology; D006224:Cricetinae; D005260:Female; D007031:Hypothalamus / Q000473:pathology* / Q000648:ultrastructure; D007515:Islets of Langerhans / Q000473:pathology* / Q000648:ultrastructure; D008647:Mesocricetus; D008854:Microscopy, Electron; D018620:PrPSc Proteins; D012608:Scrapie / Q000473:pathology*
chemical_list: D018620:PrPSc Proteins