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The Analysis of Purkinje Cell Dendritic Morphology in Organotypic Slice Cultures
Published on: March 21, 2012
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Early increase and late decrease of purkinje cell dendritic spine density in prion-infected organotypic mouse
Jody L Campeau1, Gengshu Wu, John R Bell
1Centre for Prions and Protein Folding Diseases, University of Alberta, Edmonton, Canada.
Plos One
|December 7, 2013
Summary
Prion diseases cause neurodegeneration. This study shows prion-infected mouse brain slice cultures develop early pathological changes, including dendritic spine loss, mirroring in vivo prion disease.
Area of Science:
- Neuroscience
- Prion Biology
- Cellular Pathology
Background:
- Prion diseases are fatal neurodegenerative disorders.
- Protease-resistant prion protein accumulation drives pathology.
- Early in vivo changes include dendritic spine loss.
Purpose of the Study:
- To investigate if prion-infected organotypic slice cultures recapitulate early in vivo neuropathology.
- To examine dendritic spine loss and morphology changes in this model.
- To assess the utility of slice cultures for studying early prion pathogenesis.
Main Methods:
- Infection of tga20 mouse cerebellar slice cultures with RML prion strain.
- Monitoring for protease-resistant prion protein.
- Quantifying Purkinje cell dendritic spine density and morphology at six weeks.
Main Results:
- Statistically significant loss of Purkinje cell dendritic spines observed.
- Altered dendritic morphology in infected cultures, analogous to in vivo findings.
- Transient increase in dendritic spine density upon initial prion detection.
Conclusions:
- Prion organotypic slice cultures recapitulate key early neuropathological features of prion disease.
- This model system is suitable for studying the earliest stages of prion pathogenesis.
- The findings support the use of slice cultures to investigate mechanisms of prion-induced neurodegeneration.
