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Updated: Jun 14, 2026
Detection of Abnormal Prion Protein by Immunohistochemistry
Published on: May 5, 2023
Evaluation of prion deposits and microglial activation in scrapie-infected mice using molecular imaging probes
Pu-Jiao Song1, Céline Barc, Nicolas Arlicot
1INSERM U930, Tours, France.
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.
Conclusions:
These findings indicate the ability of [(125)I]-IMPY and [(125)I]-CLINDE to evaluate prion deposits and microglial activation in vitro and ex vivo in scrapie-infected mice at different stages of the disease.
Insights
Specific ligands targeting the 18-kDa translocator protein (TSPO) effectively evaluated prion deposits and microglial activation in prion disease models. This research demonstrates TSPO ligands
Area of Science:
- Neuroscience
- Immunology
- Radiochemistry
Background:
- Prion diseases are characterized by PrP amyloid fibril aggregation in the brain, triggering chronic neuroinflammation.
- Microglial activation is a hallmark of this inflammatory response in prion diseases.
- The 18-kDa translocator protein (TSPO) is a marker of neuroinflammation, particularly microglial activation.
Purpose of the Study:
- To investigate the potential of specific 18-kDa translocator protein (TSPO) ligands for evaluating microglial activation associated with PrP(sc) deposits in prion disease.
- To assess the utility of novel radioligands for in vitro and ex vivo imaging of prion-related neuroinflammation.
Main Methods:
- In vitro autoradiography using [(3)H]-PK11195 and [(125)I]-IMPY on brain sections from scrapie-infected and control mice.
- Histoblot staining with anti-prion protein antibodies to confirm PrP(sc) deposition.
- Ex vivo autoradiography with [(125)I]-CLINDE and [(125)I]-IMPY at the terminal stage of prion disease.
Main Results:
- PrP(sc) deposits were co-localized with activated microglia as early as 60 days post-inoculation.
- Progressive PrP(sc) and TSPO staining correlated with disease progression in the hippocampus, cortex, and thalamus.
- Significant ex vivo TSPO labeling was observed in key brain regions of infected mice, though [(125)I]-IMPY showed high background.
Conclusions:
- [(125)I]-IMPY and [(125)I]-CLINDE demonstrated efficacy in evaluating prion deposits and associated microglial activation.
- These TSPO ligands show promise for in vitro and ex vivo assessment of prion disease stages.
- The findings support the use of TSPO-targeted imaging agents for prion disease research.
