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Pathways and mechanisms in the spread of prpsc to the central nervous system

Objective

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 Scheme

CSC - Cost-sharing contracts
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Coordinator

FACULTY OF MEDICINE/UNIVERSITY HOSPITAL GOETTINGEN
Address
Robert-koch-strasse 40
37075 Goettingen
Germany

Participants (5)

COMMISSARIAT A L'ENERGIE ATOMIQUE
France
Address
60-68,Route Du Panorama 18
92265 Fontenay Aux Roses
INSTITUTE FOR ANIMAL HEALTH
United Kingdom
Address
Compton Laboratory
RG20 7NN Newbury
ROBERT KOCH-INSTITUT
Germany
Address
Nordufer 20
13353 Berlin
UNIVERSITE DE LIEGE
Belgium
Address
Rue Des Pitteurs 20
4020 Liege
UNIVERSITY OF BOLOGNA
Italy
Address
Via Ugo Foscolo 7
40123 Bologna