Reflections on Cerebellar Neuropathology in Classical Scrapie

Abstract

In this review, the most important neuropathological changes found in the cerebella of sheep affected by classical natural scrapie are discussed. This disease is the oldest known of a group of unconventional “infections” caused by toxic prions of different origins. Scrapie is currently considered a “transmissible spongiform encephalopathy” (due to its neuropathological characteristics and its transmission), which is the paradigm of prion pathologies as well as many encephalopathies (prion-like) that present aberrant deposits of insoluble protein with neurotoxic effects due to errors in their catabolization (“misfolding protein diseases”). The study of this disease is, therefore, of great relevance. Our work data from the authors’ previous publications as well as other research in the field. The four most important types of neuropathological changes are neuron abnormalities and loss, neurogliosis, tissue vacuolization (spongiosis) and pathological or abnormal prion protein (PrP) deposits/deposition. These findings were analyzed and compared to other neuropathologies. Various aspects related to the presentation and progression of the disease, the involution of different neuronal types, the neuroglial responses and the appearance of abnormal PrP deposits are discussed. The most important points of controversy in scrapie neuropathology are presented.

Anatomy of hypothalamic and diencephalic nuclei involved in seasonal fertility regulation in ewes

“…Calcium-binding protein cell phenotype analysis across a high number of representative mammalian species showed that the types of positive neurons generally coincided among species. Previous analysis indicated that these proteins have a highly phylogenetically conserved molecular structure in the brain in general and in the cerebellum in particular ( 30 , 43 , 44 ). Thus, superior colliculus and cerebellum ( Supplementary Figure 1 ) have been analyzed as positive controls, showing immunostaining properties similar to those reported for humans and other high mammals, such as the common marmoset ( 29 ).…”

The Translational Benefits of Sheep as Large Animal Models of Human Neurological Disorders

“…Additionally, because ovine disease models are less well established than rodents, there are fewer validated sheep-specific neurological and cognitive tests available. Availability of reagents specialized for use on sheep tissue, particularly antibodies, is also limited, although this is improving as studies on sheep have become more common in recent years ( 60 , 124 ). In addition, because the homology between sheep and human genomes is relatively high (>85%), often antibodies developed for use on human tissue will also bind to sheep tissue.…”