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Scrapie inoculation of mice: light and electron microscopy of the superior colliculi
M Jeffrey1, J R Scott, H Fraser
1Lasswade Veterinary Laboratory, Bush Estate, Penicuik, Great Britain.
Abstract:
Ultrastructural examination of the superior colliculi of mice intraocularly inoculated with the ME7 strain of scrapie showed vacuolation early in the course of infection. Brains were examined between 85-260 days after monocular inoculation with scrapie. The mean incubation period for the development of clinical disease was 302 days. Vacuolation was seen initially in the contralateral superior colliculus and subsequently in the ipsilateral colliculus. In coded trials light microscopical vacuolation was seen from 218 days but ultrastructural examination showed that sparse vacuoles were inconsistently present in either or both of the ipsilateral and contralateral colliculi from 85 days; frequent vacuoles were seen from 190 days. Scrapie-induced vacuoles were differentiated from vacuoles present in control tissue by the presence of loculation or by a limiting double membrane which showed protrusion or proliferation of the innermost lamella. Vacuolation was seen in neuronal perikarya, myelinated fibres, dendrites and axonal presynaptic terminals. Vacuoles of myelinated fibres were observed within myelin and possibly also in the inner tongue of oligodendroglial cytoplasm. Whorled membrane configurations were also seen. Tubulovesicular particles, 40 nm in diameter, were recognised in two scrapie-infected mice. It is suggested that some scrapie vacuoles arise as a result of incorporation of abnormal membrane into organelles, possibly mitochondria, in neuronal perikarya and neurites and probably also within oligodendroglial cytoplasm and myelin.
Insights
Early ultrastructural changes in scrapie involve vacuolation in mouse superior colliculi. These vacuoles, appearing from 85 days post-infection, differ from control tissues and originate from abnormal membrane incorporation.
Area of Science:
- Neuroscience
- Pathology
- Prion Diseases
Background:
- Scrapie is a transmissible spongiform encephalopathy.
- The superior colliculi are key brain regions involved in visual processing.
- Understanding early pathological changes is crucial for disease progression studies.
Purpose of the Study:
- To investigate the early ultrastructural changes in the superior colliculi of mice infected with the ME7 scrapie strain.
- To characterize the morphology and origin of vacuoles in scrapie-infected brain tissue.
Main Methods:
- Ultrastructural examination (electron microscopy) of mouse superior colliculi.
- Intraocular inoculation with the ME7 strain of scrapie.
- Examination of brain tissue at various time points (85-260 days post-inoculation).
Main Results:
- Vacuolation was observed in the superior colliculi as early as 85 days post-inoculation, preceding clinical signs.
- Scrapie-induced vacuoles exhibited unique features, including loculation or a limiting double membrane.
- Vacuoles were found in various neuronal and glial compartments, including neuronal perikarya, myelinated fibers, dendrites, and axonal terminals.
Conclusions:
- Ultrastructural vacuolation in the superior colliculi is an early event in ME7 scrapie infection in mice.
- The findings suggest that scrapie vacuoles may form through the incorporation of abnormal membranes into cellular organelles.
- These early ultrastructural changes provide insights into the pathogenesis of prion diseases.