Neuronal spread of scrapie agent and targeting of lesions within the retino-tectal pathway

Abstract

Scrapie is a transmissible encephalopathy of sheep and goats, and a number of mammalian species can be infected experimentally. Various strains of the transmissible agent are distinguishable on pathological and biological grounds in inbred mice^1–3. The agents replicate in a variety of tissues, such as those of the lympho-reticular systems^1,4,5, but their pathological effects are confined to the central nervous system (CNS). The type, distribution and local intensity of the brain lesions vary, depending mainly on the agent strain, host genotype, route of infection and dose of agent. The principal type of lesion is vacuolar degeneration, typically with a bilaterally symmetrical distribution⁶. (Exceptional reports of its asymmetry can be attributed to ‘class III’ strains of agent⁷, none of which is used in the present study.) Whether spread of infection around the body involves the migration of infected cells, the agent passing from infected to adjacent uninfected cells, or via a possible viraemic phase to cells remote from infected foci^8,9, or transport over considerable distances along nerves, possibly with trans-synaptic infection, is not known. There is evidence that infection spreads in the CNS from the thoracic spinal cord posteriorly and to the brain^10,11, but it is still unknown whether the spread is partly or exclusively via neurones, and which types of cell are infected. The finding that the retina became infected following intracerebral injection¹² has been interpreted as evidence for neural spread but this is not conclusive because it can be shown that tracers, for example, can travel from the subarachnoid space into the perineural space of the optic nerve to the epi-choroidal and episcleral tissues of the eyeball1^3–15. I have now investigated whether lesions and infectivity can be targeted into a sensory nucleus following injection into a sense organ on one side of the body with the ipsilateral organ and nucleus acting as controls. The results show that scrapie agent can spread over a considerable distance along a nerve pathway.