The work aims to study the pathways and mechanisms of uptake, neuroinvasion and spread of PrPSc to the CNS in conventional and transgenic rodent models for TSEs. Histological and biochemical methods will be used to elucidate the temporal- spatial course and the mechanisms of progressing PrPSc deposition. Functional studies will include stimulation of B lymphocytes, vagotomy, sympathectomy and pharmacological blocking of slow axonal transport. This is expected to characterise the contacts between LRS and PNS at sites of and the role of B lymphocytes for neuroinvasion, to prove that vagus and splanchnic nerves mediate CNS invasion after oral infection, to identify components and mechanisms mediating spread along nerves, to establish murine models mimicking spread of PrPSc in sheep and cattle, to elucidate PrPSc paths after parenteral challenge and to correlate the phenotype of spread with molecular properties of PrPSc.
Funding SchemeCSC - Cost-sharing contracts
92265 Fontenay Aux Roses
RG20 7NN Newbury