Prions induce an early Arc response and a subsequent reduction in mGluR5 in the hippocampus Article Swipe
Daniel Ojeda-Juárez
,
Jessica Lawrence
,
Katrin Soldau
,
Donald Pizzo
,
Emily C. Wheeler
,
Patricia Aguilar‐Calvo
,
Helen Khuu
,
Joy Chen
,
Adela Malik
,
Gail Funk
,
Percival Nam
,
Henry Sánchez
,
Michael D. Geschwind
,
Chengbiao Wu
,
G Yeo
,
Xu Chen
,
Gentry N. Patrick
,
Christina J. Sigurdson
·
YOU?
·
· 2022
· Open Access
·
· DOI: https://doi.org/10.1016/j.nbd.2022.105834
YOU?
·
· 2022
· Open Access
·
· DOI: https://doi.org/10.1016/j.nbd.2022.105834
Synapse dysfunction and loss are central features of neurodegenerative diseases, caused in part by the accumulation of protein oligomers. Amyloid-β, tau, prion, and α-synuclein oligomers bind to the cellular prion protein (PrPC), resulting in the activation of macromolecular complexes and signaling at the post-synapse, yet the early signaling events are unclear. Here we sought to determine the early transcript and protein alterations in the hippocampus during the pre-clinical stages of prion disease. We used a transcriptomic approach focused on the early-stage, prion-infected hippocampus of male wild-type mice, and identify immediate early genes, including the synaptic activity response gene, Arc/Arg3.1, as significantly upregulated. In a longitudinal study of male, prion-infected mice, Arc/Arg-3.1 protein was increased early (40% of the incubation period), and by mid-disease (pre-clinical), phosphorylated AMPA receptors (pGluA1-S845) were increased and metabotropic glutamate receptors (mGluR5 dimers) were markedly reduced in the hippocampus. Notably, sporadic Creutzfeldt-Jakob disease (sCJD) post-mortem cortical samples also showed low levels of mGluR5 dimers. Together, these findings suggest that prions trigger an early Arc response, followed by an increase in phosphorylated GluA1 and a reduction in mGluR5 receptors.
Related Topics
Concepts
Arc (geometry)
Metabotropic glutamate receptor 5
Metabotropic glutamate receptor
Hippocampus
Synapse
Biology
Glutamate receptor
AMPA receptor
Receptor
Neuroscience
Downregulation and upregulation
Cell biology
Gene
Genetics
Mathematics
Geometry
Metadata
- Type
- article
- Language
- en
- Landing Page
- https://doi.org/10.1016/j.nbd.2022.105834
- OA Status
- gold
- Cited By
- 11
- References
- 76
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W4288045859
All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
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https://openalex.org/W4288045859Canonical identifier for this work in OpenAlex
- DOI
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https://doi.org/10.1016/j.nbd.2022.105834Digital Object Identifier
- Title
-
Prions induce an early Arc response and a subsequent reduction in mGluR5 in the hippocampusWork title
- Type
-
articleOpenAlex work type
- Language
-
enPrimary language
- Publication year
-
2022Year of publication
- Publication date
-
2022-07-26Full publication date if available
- Authors
-
Daniel Ojeda-Juárez, Jessica Lawrence, Katrin Soldau, Donald Pizzo, Emily C. Wheeler, Patricia Aguilar‐Calvo, Helen Khuu, Joy Chen, Adela Malik, Gail Funk, Percival Nam, Henry Sánchez, Michael D. Geschwind, Chengbiao Wu, G Yeo, Xu Chen, Gentry N. Patrick, Christina J. SigurdsonList of authors in order
- Landing page
-
https://doi.org/10.1016/j.nbd.2022.105834Publisher landing page
- Open access
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YesWhether a free full text is available
- OA status
-
goldOpen access status per OpenAlex
- OA URL
-
https://doi.org/10.1016/j.nbd.2022.105834Direct OA link when available
- Concepts
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Arc (geometry), Metabotropic glutamate receptor 5, Metabotropic glutamate receptor, Hippocampus, Synapse, Biology, Glutamate receptor, AMPA receptor, Receptor, Neuroscience, Downregulation and upregulation, Cell biology, Gene, Genetics, Mathematics, GeometryTop concepts (fields/topics) attached by OpenAlex
- Cited by
-
11Total citation count in OpenAlex
- Citations by year (recent)
-
2025: 6, 2024: 3, 2023: 2Per-year citation counts (last 5 years)
- References (count)
-
76Number of works referenced by this work
- Related works (count)
-
10Other works algorithmically related by OpenAlex
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