Prion diseases are fatal neurodegenerative diseases of humans and animals. Dissemination in the nervous system occurs by prion agent movement along nerve fibers and transynaptic spread between neurons. The long-term goal of the proposed research is to define the mechanism of prion agent transport in the nervous system. These events are central to understanding the pathogenesis of prion diseases, but the mechanism of prion dissemination within the nervous system is not well understood. In this application, in vivo and in vitro models will be used to investigate transynaptic and axonal transport of prions. The neuromuscular junction, a peripheral synapse, will be used to study transynaptic spread of prions between peripheral nerves and skeletal muscle cells in vivo, and in mixed neuron-muscle co-cultures in vitro. These studies can identify the role of the neuromuscular junction in the spread of the prion agent to peripheral tissues and provide an in vitro model to investigate cellular pathways involved in transneuronal spread in the nervous system. To investigate the pathway of prion movement in neurons, studies will investigate the spread of prions between the brain and nasal mucosa within olfactory receptor neurons. These studies can determine the role of the olfactory nerve in centrifugal prion spread to the nasal mucosa where agent shedding is a potential route of prion transmission.

Public Health Relevance

Prion diseases are fatal neurodegenerative diseases of humans and animals that can be transmitted vertically as well as horizontally through environmental contamination, ingestion of contaminated food, or by accidental exposure during medical procedures. These studies will investigate the mechanism of prion agent spread in the nervous system since this is a central event in dissemination within a host and necessary for transmission. Identification of the cellular pathways involved in prion transport can lead to the development of therapeutic interventions that can prevent disease dissemination.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
2R01AI055043-06A2
Application #
7580291
Study Section
Special Emphasis Panel (ZRG1-IDM-Q (92))
Program Officer
Beisel, Christopher E
Project Start
2003-06-01
Project End
2013-11-30
Budget Start
2008-12-01
Budget End
2009-11-30
Support Year
6
Fiscal Year
2009
Total Cost
$178,125
Indirect Cost
Name
Montana State University - Bozeman
Department
Veterinary Sciences
Type
Schools of Earth Sciences/Natur
DUNS #
625447982
City
Bozeman
State
MT
Country
United States
Zip Code
59717
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