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Updated: Jun 20, 2026
10:26
Monitoring Cell-to-cell Transmission of Prion-like Protein Aggregates in Drosophila Melanogaster
Published on: March 12, 2018
Degenerating synaptic boutons in prion disease: microglia activation without synaptic stripping
Zuzana Sisková1, Anton Page, Vincent O'Connor
1CNS Inflammation Group, Basset Crescent East, School of Biological Sciences, University of Southampton, Southampton SO16 7PX, UK. z.siskova@soton.ac.uk.
The American Journal of Pathology
|September 26, 2009
Summary
Synaptic loss in prion disease is a neuron-autonomous event, occurring without direct glial cell involvement. This finding offers new insights into neurodegenerative disease mechanisms and potential therapeutic targets.
Area of Science:
- Neuroscience
- Pathology
- Cell Biology
Background:
- Synaptic loss is an early hallmark of neurodegenerative diseases.
- Murine prion disease models allow study of chronic neurodegeneration.
- Previous work indicated selective presynaptic element loss and microglial activation.
Purpose of the Study:
- To investigate the mechanisms of synaptic loss in prion disease.
- To determine the role of microglia in synaptic degeneration.
- To elucidate whether synaptic loss is neuron-autonomous or glial-mediated.
Main Methods:
- Analysis of synaptic density in murine prion disease models.
- Three-dimensional reconstructions using Dual Beam electron microscopy.
- Examination of microglia-synapse interactions.
Main Results:
- Progressive synaptic loss was observed starting 12 weeks post-disease initiation.
- Synaptic loss was not associated with microglia processes.
- Postsynaptic densities wrapped around degenerating presynaptic elements, indicating a neuron-autonomous process.
Conclusions:
- Synaptic loss in prion disease is a neuron-autonomous event.
- Glial cells, including microglia, are not directly involved in this synaptic stripping.
- Neuron engulfment of degenerating synapses may contribute to synaptic changes in development and disease.
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