Award details

PrPSc-nEUROpathways

Reference	BBS/E/I/00000969
Principal Investigator / Supervisor	Mrs Patricia McBride
Co-Investigators / Co-Supervisors
Institution	The Pirbright Institute
Department	The Pirbright Institute Department
Funding type	Research
Value (£)	52,213
Status	Completed
Type	Institute Project
Start date	01/09/2002
End date	31/03/2007
Duration	55 months

Abstract

TSEs are neurodegenerative diseases. However natural exposure to their causal agents is extracerebral with infection via the gastrointestinal tract being a highly probable route of entry for scrapie, BSE, vCJD, FSE and CWD. In the past experimental rodent models of scrapie were established to investigate the spread of PrPSc after oral challenge. These have provided substantial evidence that the pathway of infection is via the enteric nervous system along autonomic fibers of the splanchnic and vagus nerve to the central nervous system (CNS), and that the gut-associated lymphoid tissue is an early replication site of PrPSc after uptake of infectivity via the gastrointestinal tract. The overall aim of the PrPSc-nEUROpathways project is to study pathways and mechanisms related to cellular uptake, formation, neuroinvasion and spread of PrPSc in rodent models for transmissible spongiform encephalopathies (TSEs). The pathways and mechanisms in the spread of PrPSc to the central nervous system will be addressed in scrapie-challenged hamsters and mice and in a murine model of bovine spongiform encephalopathy (BSE). Specifically, this project will address the following aspects of peripheral pathogenesis: neuro-immune interfaces and transfer of PrPSc from the lymphoreticular to the peripheral nervous system; the impact of B lymphocyte activation on neuroinvasion; the influence of vagotomy and sympathectomy on the spread of PrPSc after oral infection: neural components and mechanisms mediating the spread of PrPSc along peripheral nerves; spreading pathways following parenteral infection; mouse models for the spread of PrPSc and the physico-chemical properties of PrPSc and phenotypic spread of infection.

Summary

unavailable

Committee	Closed Committee - Agri-food (AF)
Research Topics	X – not assigned to a current Research Topic
Research Priority	X – Research Priority information not available
Research Initiative	X - not in an Initiative
Funding Scheme	X – not Funded via a specific Funding Scheme

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