Evaluation of prion deposits and microglial activation in scrapie-infected mice using molecular imaging probes.
OBJECTIVE
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.


METHODS
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.
Song
Pu-Jiao
PJ
INSERM U930, Tours, France.
Barc
Céline
C
Arlicot
Nicolas
N
Guilloteau
Denis
D
Bernard
Serge
S
Sarradin
Pierre
P
Chalon
Sylvie
S
Garreau
Lucette
L
Kung
Hank F
HF
Lantier
Frédéric
F
Vergote
Jackie
J
D000818:Animals; D001345:Autoradiography; D001921:Brain / Q000000981:diagnostic imaging / Q000378:metabolism; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000493:pharmacokinetics; D007457:Iodine Radioisotopes / Q000493:pharmacokinetics; D051379:Mice; D008810:Mice, Inbred C57BL; D017628:Microglia / Q000378:metabolism* / Q000473:pathology; D057054:Molecular Imaging / Q000379:methods*; D015335:Molecular Probes / Q000493:pharmacokinetics; D058225:Plaque, Amyloid / Q000000981:diagnostic imaging / Q000378:metabolism; D011328:Prions / Q000032:analysis / Q000378:metabolism*; D011725:Pyridines; D011877:Radionuclide Imaging; D012608:Scrapie / Q000000981:diagnostic imaging* / Q000378:metabolism / Q000473:pathology
C504993:6-chloro-2-(4'-iodophenyl)-3-(N,N-diethyl)imidazo(1,2-a)pyridine-3-acetamide; C473191:6-iodo-2-(4'-dimethylamino-)phenyl-imidazo(1,2-a)pyridine; D019086:Bridged Bicyclo Compounds, Heterocyclic; D007457:Iodine Radioisotopes; D015335:Molecular Probes; D011328:Prions; D011725:Pyridines