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Published on: November 19, 2010
Infection route-independent accumulation of splenic abnormal prion protein
Yuji Inoue1, Yoshio Yamakawa, Akikazu Sakudo
1Department of Molecular Immunology, School of Agricultural and Life Sciences, University of Tokyo, Tokyo 113-8657, Japan.
Abstract:
The accumulation kinetics of the abnormal form of prion protein (PrP(Sc)) in spleens and brains of scrapie (Obihiro-1)-infected mice at various times after intracerebral (i.c.), intraperitoneal (i.p.), or oral inoculation were studied. PrP(Sc) was first detected by Western blotting with anti-prion protein antibodies on days 70 and 116 after i.c. (3 microg) in spleens and brains, respectively. Although the amount of cerebral PrP(Sc) gradually increased to the maximum level on day 152 after i.c. inoculation, splenic PrP(Sc) established the maximum level on day 116 after i.c. inoculation then registered slight decreases up to day 152 with further incubation. The detectable levels of cerebral PrP(Sc) by Western blotting were established on day 231 or 259, whereas those of splenic PrP(Sc) were detected on day 94 or 93, after i.p. and oral infection, respectively. The splenic PrP(Sc) decreased slightly thereafter. These results indicate that splenic PrP(Sc) increased before cerebral PrP(Sc) established a detectable level in a manner independent of the inoculation route.
Insights
The abnormal prion protein (PrPSc) accumulates in mouse spleens before the brain, regardless of infection route. This splenic PrPSc increase precedes detectable brain PrPSc levels in scrapie models.
Area of Science:
- Neuroscience
- Immunology
- Biochemistry
Background:
- Prion diseases, like scrapie, are characterized by the accumulation of abnormal prion protein (PrPSc).
- Understanding the kinetics of PrPSc accumulation is crucial for disease progression and potential therapeutic interventions.
Purpose of the Study:
- To investigate the accumulation kinetics of PrPSc in spleens and brains of mice infected with scrapie (Obihiro-1 strain).
- To compare PrPSc accumulation patterns following different inoculation routes: intracerebral (i.c.), intraperitoneal (i.p.), and oral.
Main Methods:
- Mice were inoculated with scrapie via i.c., i.p., or oral routes.
- PrPSc accumulation was monitored over time using Western blotting with anti-prion protein antibodies.
- Detection of PrPSc in spleen and brain tissues at various post-inoculation time points.
Main Results:
- PrPSc was first detected in spleens by day 70 and in brains by day 116 after i.c. inoculation.
- Splenic PrPSc peaked earlier (day 116) than cerebral PrPSc (day 152) following i.c. infection.
- Detectable PrPSc levels in spleen appeared earlier (days 93-94) than in brain (days 231-259) after i.p. and oral inoculation.
Conclusions:
- Splenic PrPSc accumulation precedes detectable cerebral PrPSc accumulation.
- The observed splenic PrPSc increase occurs independently of the inoculation route.
- These findings highlight the spleen as an early site for PrPSc propagation in scrapie infection.
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