EARLY LOSS OF NEURONS AND AXON TERMINALS IN SCRAPIE-AFFECTED MICE REVEALED BY MORPHOMETRY AND IMMUNOCYTOCHEMISTRY

This study demonstrates that an unsuspected and dramatic neuronal loss occurs in the dLGN of mice intraocularly infected with ME7 scrapie, up to 100 d before clinical signs are apparent. The onset of detectable neuronal loss has a close correlation with the onset of vacuolation. Since a similar loss has been shown in cattle affected with BSE, it suggests that neuronal loss is a consistent feature of the pathology of these and other spongiform encephalopathies. The extent of vacuolar pathology is well recognized in these diseases, and although an associated “slight neuronal loss” is often quoted, we have shown that the degree of neuronal loss cannot be estimated by subjective analysis, except in extremely severe cases. The genesis and progression of the vacuolation is not known, nor is the extent to which this lesion compromises neuronal function. Several clinical cases of various spongiform encephalopathies have been reported that show little or no vacuolation (Taylor, 1991). It is possible, therefore, that moderate neuronal loss has a closer correlation with clinical diseases than has been recognized. Ultrastructural studies on primary transmissions of spongiform encephalopathy to mice have revealed conspicuous neuronal autophagy (Jeffrey et al., 1992c), which, together with the recognized absence of inflammatory changes with this disease, suggests an apoptotic rather than necrotic mechanism of neuronal loss. © 1995, Humana Press Inc.. All rights reserved.