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Targeting of scrapie lesions and spread of agent via the retino-tectal projection
Abstract:
Scrapie infectivity and degenerative vacuolation was initially localized within the contralateral superior colliculus following intraocular injection. The time course of these events was prolonged. With the ME7 strain of scrapie in Sincs7 genotype mice, infectivity began to rise in the superior colliculus from about 70 days, followed by the earliest asymmetrical lesions there from 120 days, with death occurring at about 250 days, at which time vacuolar degeneration was widespread in the brain. With other mouse Sinc genotype mouse/agent strain combinations the process was even further prolonged. With 87V scrapie strain in Sincp7 genotype mice the first lesions to appear were in the contralateral tectum at 300 days. It is concluded that scrapie agent can spread within ganglion cell axons.
Insights
Scrapie infectivity spreads via ganglion cell axons, initially affecting the superior colliculus after eye injection. Lesion development and disease progression vary by mouse genotype and scrapie strain.
Area of Science:
- Neuroscience
- Prion Diseases
- Ophthalmology
Background:
- Scrapie is a transmissible spongiform encephalopathy.
- The initial site of scrapie agent entry and spread is crucial for understanding pathogenesis.
- Intraocular injection provides a direct route to the central nervous system.
Purpose of the Study:
- To investigate the initial localization and spread of scrapie infectivity and pathology following intraocular injection.
- To characterize the time course of scrapie pathogenesis in different mouse models.
- To determine if scrapie agent can spread within ganglion cell axons.
Main Methods:
- Intraocular injection of scrapie agent (ME7 and 87V strains) into mice with different Sinc genotypes (Sincs7 and Sincp7).
- Monitoring of scrapie infectivity and vacuolar degeneration in the superior colliculus and other brain regions over time.
- Histopathological analysis to identify and quantify lesions.
Main Results:
- Scrapie infectivity and vacuolar degeneration were initially localized in the contralateral superior colliculus post-intraocular injection.
- The time course of lesion development and disease progression was prolonged and dependent on the mouse Sinc genotype and scrapie strain.
- ME7 scrapie in Sincs7 mice showed rising infectivity around 70 days, lesions at 120 days, and widespread degeneration by 250 days.
- 87V scrapie in Sincp7 mice exhibited initial lesions in the contralateral tectum at 300 days.
Conclusions:
- The scrapie agent can spread within ganglion cell axons from the eye to the brain.
- The superior colliculus is an early site of scrapie replication and pathology after ocular inoculation.
- Mouse Sinc genotype and agent strain significantly influence the kinetics of scrapie pathogenesis.