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Title: The pathogenesis of 263K scrapie in Syrian hamsters following oral infection
Author: McBride, Patricia
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 2004
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The main aim of this project was to define the neuroanatomical pathways by which the infectious agent gained access to the brain and spinal cord after oral challenge of hamsters with 263K scrapie. Immunocytochemistry, paraffin-embedded tissue blotting and selective bioassays of agent were used to identify the location and temporal sequence of disease-associated PrP (PrPd) accumulation in the CNS, PNS and enteric nervous system (ENS) of hamsters. Invasion of the brain occurred directly via the vagus nerve rather than by spreading along the spinal cord. The infectious agent reached the CNS simultaneously by two pathways. One route accessed the thoracic spinal cord via the intermediolateral cell column and another entered the dorsal motor nucleus of the vagus of the brain. Thereafter spread occurred between interconnected neurones. By identifying and quantifying the presence of PRPd in the CNS, vagal and splanchnic nerve circuitry and the GI tract, it was possible to precisely identify routes and timing of neuroanatomical spread. PrPd accumulated, in sequence, in target sites that accurately reflected known autonomic and sensory relays. PrPd  was observed in enteric and autonomic neurones prior to sensory neurones suggesting that the infectious agent primarily utilised synaptically-linked autonomic ganglia and efferent fibres to invade the CNS. Infectivity was present in the PNS at low to moderate levels. Therefore, after ingestion of 263K scrapie, the PNS and specifically, autonomic components of the vagus and splanchnic nerves are important in conveying the infectious agent to target sites in the CNS. The temporal interaction between lymphoid cells (follicular dendritic cells, macrophages, dendritic cells and Peyer’s patch epithelium) and enteric neurones suggested that lymphoid elements are sequentially involved in PrPd processing. Existing evidence is compatible with the LRS being an optional mediator rather than a key player in neuroinvasion in this experimental model.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available