Neuropathology of ovine ceroid-lipofuscinosis : a thesis presented in partial fulfilment (30%) of the requirements for the degree of Master of Philosophy in Veterinary Pathology at Massey University

Abstract

The purposes of this study were to describe the neuropathology of ovine ceroid-lipofuscinosis, to compare findings with those of the related entities in humans and other domestic animals, and to provide morphological information that might help elucidate the pathogenesis of these diseases. An established flock of South Hampshire sheep carrying the ceroid-lipofuscinosis gene have made it possible to perform a longitudinal study on the central nervous system of affected sheep of various ages including foetuses. The most striking gross pathological change of affected sheep was brain atropy. At terminal disease, the brain weights of affected sheep were 55% of those of normal sheep. Atrophy affected mainly the cerebrum. Sudan black and luxol fast blue positive autofluorescent neuronal pigment granules were detected by lightmicroscopy as early as the mid stage of foetal development, the earliest stage examined. Postnatally there were topographical differences in the quantity of accumulated lipopigments in neurones of various areas. Similarly, there were age related topographical differences in secondary degenerative changes. Neuronal loss was most severe in the parietal lobe cortex showing an initial laminar distribution. This pattern was well demonstrated by a concomitant astrocytosis. In addition to the complex electron dense cytosomes similar to those reported in the human syndromes, there were less complex cytosomes of smaller size in affected foetal brains. The latter were clearly bounded by a trilaminar membrane and contained whorls or loose stacks of trilaminar membranes resembling those of the limiting membranes. In some electronmicrographs there was a suggestion of continuity between the surrounding membrane and the internal membranes, but this was not definitely demonstrated. This is provisionally interpreted as being due to an internalization of surrounding limiting membrane rather than a recycling of membrane. Some of these small cytosomes also showed complex multilamellar profiles similar to those of large complex cytosomes. These latter appeared to be formed by coalescence of smaller complex ones. There thus appeared to be a sequence of changes in the development of storage cytosomes. This study revealed that the ovine disease has not only many neuropathological findings in common with analogous human diseases, but also some pathological features which have not been reported in affected humans or animals. Ovine ceroid-lipofuscinosis is thus a useful animal model for the study of the human ceroid-lipofuscinoses.