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Updated: Jul 31, 2026
Monitoring Astrocyte Reactivity and Proliferation in Vitro Under Ischemic-Like Conditions
Published on: October 21, 2017
A prion protein fragment primes type 1 astrocytes to proliferation signals from microglia
D R Brown1, B Schmidt, H A Kretzschmar
1MRC Cambridge Centre for Brain Repair, University of Cambridge, United Kingdom.
Abstract:
Giliosis is a hallmark of prion disease. A neurotoxic prion peptide (PrP106-126) induces astrocyte proliferation in the presence of microglia. This peptide also directly enhances microglial proliferation in culture. We have investigated this further to understand the method by which factors released by microglia and PrP106-126 work together to enhance astrocyte proliferation. PrP106-126 in the presence of microglia specifically enhanced type 1 astrocyte proliferation but not Type 2. Astrocytes that do not express the prion protein were more sensitive to oxidative stress and the toxicity of cytosine arabinoside. In the presence of cytosine arabinoside, PrP106-126 was toxic to pure astrocyte cultures. Using conditioned medium from microglia we have shown that PrPc-expressing astrocytes proliferate in response to factors released by microglia stimulated by granulocyte/macrophage colony-stimulating factor. This response is enhanced in the presence of PrP106-126. PrPc-deficient astrocytes do not show this response. These results suggest that astrocytes are primed by PrP106-126 to respond more to factors released by proliferating microglia. Astrocytes may proliferate in this system to escape entering the cell suicide pathway.
Insights
Prion peptide PrP106-126 enhances astrocyte proliferation by priming them to respond to microglial factors. This interaction may help astrocytes evade cell death pathways during prion disease.
Area of Science:
- Neuroscience
- Cell Biology
- Prion Disease Research
Background:
- Gliois is a key feature of prion diseases.
- Neurotoxic prion peptides, like PrP106-126, are implicated in disease pathogenesis.
- PrP106-126 can induce astrocyte and microglial proliferation.
Purpose of the Study:
- To investigate the synergistic mechanisms between microglial factors and PrP106-126 in promoting astrocyte proliferation.
- To elucidate the role of prion protein (PrPc) expression in astrocyte responses.
- To understand astrocyte proliferation as a potential survival mechanism.
Main Methods:
- Co-culture systems involving astrocytes and microglia.
- Treatment with PrP106-126 peptide and cytosine arabinoside.
- Use of conditioned medium from stimulated microglia.
- Assessment of astrocyte proliferation and sensitivity to oxidative stress.
- Comparison of PrPc-expressing and PrPc-deficient astrocytes.
Main Results:
- PrP106-126 specifically enhanced Type 1 astrocyte proliferation in the presence of microglia.
- PrPc-deficient astrocytes showed increased sensitivity to oxidative stress and cytosine arabinoside.
- PrP106-126 rendered pure astrocyte cultures toxic in the presence of cytosine arabinoside.
- PrPc-expressing astrocytes proliferated in response to microglial factors, an effect amplified by PrP106-126.
- PrPc-deficient astrocytes did not exhibit this proliferative response.
Conclusions:
- Astrocytes are primed by PrP106-126 to enhance their proliferative response to microglial-derived factors.
- PrPc expression on astrocytes is crucial for this priming effect.
- Astrocyte proliferation induced by this interaction may serve as a protective mechanism against cell death in prion diseases.
