Developing organotypic slice culture (OSC) to model the relationship between amyloid seeding and plaque formation in vitro.

Transmissible spongiform encephalopathies (TSEs) are a group of infectious neurodegenerative diseases found in both humans and animals. The infectious agent in these diseases is the prion, the exact physical nature of which remains to be confirmed. Despite this it has been widely accepted in TSE research that a misfolded form of the endogenous prion protein (PrPSc) is the infectious agent. Although PrPSc is commonly found to accumulate in prion diseases it has been recently discovered that its accumulation in the form of amyloid plaques can occur in the absence of infectious TSE disease.
This project aims to study the mechanisms of amyloid plaque formation in real time using brain organotypic slice culture (OSC). LI-COR Odyssey and confocal imaging systems will be utilised to visualise plaque formation in brain OSCs following exposure to infectious TSE or PrP amyloid seeds.
The OSC will also be tested for TSE infectivity levels to investigate the role of amyloid plaques in TSE disease. To assess the effect of plaques on cell survival and cell viability will also be tested. Brain OSCs from wild type mice have been established in culture for approximately 60 days and cells have been shown to be viable over this time period.