Evaluation of Prion Deposits and Microglial Activation in Scrapie-Infected Mice Using Molecular Imaging Probes

• Published in: Molecular imaging and biology Vol. 12; no. 6; pp. 576 - 582
• Main Authors: Song, Pu-Jiao, Barc, Céline, Arlicot, Nicolas, Guilloteau, Denis, Bernard, Serge, Sarradin, Pierre, Chalon, Sylvie, Garreau, Lucette, Kung, Hank F., Lantier, Frédéric, Vergote, Jackie
• Format: Journal Article
• Language: English
• Published: New York Springer-Verlag 01-12-2010; Springer Nature B.V; Springer Verlag
• Subjects: Animals; Autoradiography; Brain - diagnostic imaging; Brain - metabolism; Bridged Bicyclo Compounds, Heterocyclic - pharmacokinetics; Brief Article; Imaging; Iodine Radioisotopes - pharmacokinetics; Life Sciences; Medicine; Medicine & Public Health; Mice; Mice, Inbred C57BL; Microglia - metabolism; Microglia - pathology; Molecular Imaging - methods; Molecular Probes - pharmacokinetics; Plaque, Amyloid - diagnostic imaging; Plaque, Amyloid - metabolism; Prions - analysis; Prions - metabolism; Pyridines; Radiology; Radionuclide Imaging; Scrapie - diagnostic imaging; Scrapie - metabolism; Scrapie - pathology; Molecular imaging; I]-IMPY; Prion deposit; Translocator protein (18 kDa); I]-CLINDE; [; Microglial activation; EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; ALZHEIMERS-DISEASE; [I]-CLINDE; Translocator protein (18 kDa); [I]-IMPY; MURINE SCRAPIE; POSITRON-EMISSION-TOMOGRAPHY; MULTIPLE-SCLEROSIS; NEUROINFLAMMATION; CREUTZFELDT-JAKOB; PERIPHERAL BENZODIAZEPINE-RECEPTOR; BINDING-SITES; BRAIN
• ISSN: 1536-1632; 1860-2002
• DOI: 10.1007/s11307-010-0321-1

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.