Cited by 34Prion Diseases and Protein MisfoldingNeuroinflammation and Neurodegeneration MechanismsAlzheimer's disease research and treatments

Glial activation in prion diseases is selectively triggered by neuronal PrPSc

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Lakkaraju, Asvin K. K., Sorce, Silvia, Senatore, Assunta, Nuvolone, Mario, Guo, Jingjing, Schwarz, Petra, Moos, Rita, Pelczar, Pawel +1 more·2022·Brain Pathology

Abstract

Although prion infections cause cognitive impairment and neuronal death, transcriptional and translational profiling shows progressive derangement within glia but surprisingly little changes within neurons. Here we expressed PrP C selectively in neurons and astrocytes of mice. After prion infection, both astrocyte and neuron‐restricted PrP C expression led to copious brain accumulation of PrP Sc. As expected, neuron‐restricted expression was associated with typical prion disease. However, mice with astrocyte‐restricted PrP C expression experienced a normal life span, did not develop clinical disease, and did not show astro‐ or microgliosis. Besides confirming that PrP Sc is innocuous to PrP C‐deficient neurons, these results show that astrocyte‐born PrP Sc does not activate the extreme neuroinflammation that accompanies the onset of prion disease and precedes any molecular changes of neurons. This points to a nonautonomous mechanism by which prion‐infected neurons instruct astrocytes and microglia to acquire a specific cellular state that, in turn, drives neural dysfunction.

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  • In mice that exclusively produce PrPSc in neurons or in astrocytes, neither cell type drives the dysregulation of glia cells on its own.

    “Novel research in mice that exclusively produce PrPSc in neurons or in astrocytes shows that neither drive the dysregulation of glia cells on their own [60].”

    From Loss of Homeostatic Microglia Signature in Prion Diseases (2022) · cites this paper as [60]

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Authors
Lakkaraju, A. K. K., Sorce, S., Senatore, A., Nuvolone, M., Guo, J., Schwarz, P., Moos, R., Pelczar, P., & Aguzzi, A.
Affiliations
  • University Hospital Zurich (CH)
  • University of Pavia (IT)
  • Center for Transgenic Models University of Basel Basel Switzerland
Corresponding author
Aguzzi, Adriano
Venue
Brain Pathology
Publisher
Wiley
Published
2022-02-17
Volume
32
Issue
5
Pages
e13056-e13056
ISSN
  • 1015-6305 (ISSN-L)
  • 1750-3639
OpenAlex
W4213272417
Cited by
34
References
36
Citations by year
2026: 2 · 2025: 5 · 2024: 15 · 2023: 7 · 2022: 4 · 2021: 1
FWCI
2.53
Type
journal article
Language
en
Open access
Locations
  • Brain Pathology (publishedVersion, cc-by-nc-nd)
  • PubMed Central (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
  • Zurich Open Repository and Archive (University of Zurich) (acceptedVersion, cc-by-nc-nd)
  • Zurich Open Repository and Archive (University of Zurich) (submittedVersion, cc-by-nc-nd)
  • Zurich Open Repository and Archive (University of Zurich)
Funders
  • Stiftung Synapsis - Alzheimer Forschung Schweiz AFS
  • SystemsX.ch
  • Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung
  • H2020 European Research Council
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Prion Diseases and Protein Misfolding
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
Keywords
prion disease, glial activation, PrPSc, cellular prion protein, astrocytes, microglia, neuroinflammation, prion infection
MeSH terms
Animals, Astrocytes, Neuroglia, Neurons, Prions, Prion Diseases, Mice

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