Evaluation of Prion Deposits and Microglial Activation in Scrapie-Infected Mice Using Molecular Imaging Probes
Abstract
Purpose A characteristic of prion diseases which affect both animals and humans is the aggregation of PrP amyloid fibrils in the brain, associated with a chronic inflammatory response dominated by microglial activation. In this study, we hypothesised that specific ligands of the 18-kDa translocator protein (TSPO) would be effective in the evaluation of microglial activation related to PrP(sc) deposits in prion disease. Procedures Chronological studies using in vitro autoradiography were carried out with [(3)H]-PK11195 and [(125)I]-IMPY on frozen cerebral sections from scrapie-infected mice and controls. Accumulation of prion deposits was confirmed by histoblot staining with prion protein-specific monoclonal antibody. Ex vivo autoradiographic studies were carried out with [(125)I]-CLINDE and [(125)I]-IMPY at the terminal stage of infection. Results Chronological studies using in vitro autoradiography showed that PrP(sc) deposits were co-localised with activated microglia as early as 60 days post-inoculation. Progressive levels of PrP(sc) and TSPO staining were successively observed in the hippocampus, cortex and left thalamus of infected mouse brain sections in the course of the disease and were correlated with the signals obtained by histoblot staining. Significant TSPO labelling was also observed ex vivo in the cortex, hippocampus and thalamus of scrapie-infected mice. In parallel, [(125)I]-IMPY showed labelling in the same cerebral regions but with high background staining.…
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The demonstration of increased TSPO in experimental prion disease aligns with earlier findings using the first generation TSPO radiotracer [3H]PK11195.
“This demonstration of increased TSPO in experimental prion disease aligns with ours and others’ earlier findings using the first generation TSPO radiotracer [3H]PK11195 [33, 37].”
From Pharmacological modulation of TSPO in microglia/macrophages and neurons in a chronic neurodegenerative model of prion disease (2023) · cites this paper as [37]
[3H]PBR28 binding was significantly increased in the cortex, hippocampus and thalamus of ME7 vs. NBH mice.
“[3H]PBR28 binding was significantly increased in the cortex, hippocampus and thalamus of ME7 vs. NBH mice, in line with previous findings [33, 37].”
From Pharmacological modulation of TSPO in microglia/macrophages and neurons in a chronic neurodegenerative model of prion disease (2023) · cites this paper as [37]
Cites
In vivo detection of microglial activation in frontotemporal dementia
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Positron Emission Tomography Imaging of Neuroinflammation
Cagnin, A., Kassiou, M., Meikle, S. R., & Banati, R. B. (2007) · Neurotherapeutics · doi:10.1016/j.nurt.2007.04.006 · Cited by 137 · see citing works
Van Everbroeck, B., Dobbeleir, I., De Waele, M., De Leenheir, E., Lübke, U., Martin, J.-J., & Cras, P. (2004) · Acta Neuropathologica · doi:10.1007/s00401-004-0879-2 · Cited by 66 · see citing works
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Vicente-Rodríguez, M., Mancuso, R., Peris-Yague, A., Simmons, C., NIMA Consortium, Wlazly, D., Dickinson, A., Foster, A., Knight, C., Leckey, C., et al. (2023) · Journal of Neuroinflammation · doi:10.1186/s12974-023-02769-y · Cited by 17 · see citing works
“This demonstration of increased TSPO in experimental prion disease aligns with ours and others’ earlier findings using the first generation TSPO radiotracer [3H]PK11195 [33, 37].”
Result
- Authors
- Song, P.-J., Barc, C., Arlicot, N., Guilloteau, D., Bernard, S., Sarradin, P., Chalon, S., Garreau, L., Kung, H. F., Lantier, F., & Vergote, J.
- Affiliations
- Université de Tours (FR)
- Institut National de Recherche pour l'Agriculture, l'Alimentation et l'Environnement (FR)
- University of Pennsylvania (US)
- Corresponding author
- Vergote, Jackie
- Venue
- Molecular Imaging and Biology
- Published
- 2010-04-08
- Volume
- 12
- Issue
- 6
- Pages
- 576-582
- ISSN
- 1536-1632 (ISSN-L)
- 1860-2002
- OpenAlex
- W2072021437
- Cited by
- 11
- References
- 3
- Citations by year
- 2024: 2 · 2023: 1 · 2017: 2 · 2015: 1 · 2014: 1 · 2012: 2
- FWCI
- 0.39
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Molecular Imaging and Biology (publishedVersion)
- PubMed (publishedVersion)
- HAL (submittedVersion)
- Funders
- National Institute on Aging (AG21868, R21AG021868)
- 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
- scrapie, prion disease, microglial activation, translocator protein (TSPO), TSPO ligands, PK11195, molecular imaging probes, hippocampus, thalamus, cerebral cortex
- MeSH terms
- Animals, Autoradiography, Brain, Iodine Radioisotopes, Mice, Inbred C57BL, Prions, Pyridines, Radionuclide Imaging, Scrapie, Molecular Probes, Microglia, Bridged Bicyclo Compounds, Heterocyclic, Mice, Molecular Imaging, Plaque, Amyloid
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