Accumulation of abnormal prion protein in mice infected with Creutzfeldt-Jakob disease via intraperitoneal route: a

T Muramoto1, T Kitamoto, J Tateishi

  • 1Department of Neuropathology, Faculty of Medicine, Kyushu University 60, Fukuoka, Japan.

Insights

Abnormal prion protein spreads throughout the central nervous system and lymphoid tissues in mice with Creutzfeldt-Jakob disease (CJD) following intraperitoneal infection. Early detection occurs in peripheral organs before widespread central nervous system involvement.

Area of Science:

  • Neuroscience
  • Immunology
  • Pathology

Background:

  • Creutzfeldt-Jakob disease (CJD) is a fatal neurodegenerative prion disease.
  • Understanding prion protein (PrP) distribution is crucial for diagnosing and treating CJD.
  • The intraperitoneal (IP) route of infection offers a different model for studying prion pathogenesis compared to intracerebral (IC) inoculation.

Purpose of the Study:

  • To investigate the spatiotemporal distribution of abnormal prion protein (PrPSc) in the central nervous system (CNS) and visceral organs of mice infected with CJD via the IP route.
  • To compare PrPSc distribution patterns between IP and IC infection models.
  • To determine the earliest detection times and progression of PrPSc accumulation in different tissues.

Main Methods:

  • Immunohistochemical staining was used to detect PrPSc.
  • Mice were infected with CJD via the IP route.
  • Samples from the CNS and various visceral organs (spleen, lymph nodes, Peyer's patch, thymus) were analyzed at different time points post-inoculation.

Main Results:

  • Abnormal prion protein (PrPSc) showed diffuse distribution in the CNS, with initial staining detected at 120 days post-inoculation, becoming widespread by 180 days and most intense by 270 days.
  • Unlike IC infection, IP infection did not show restricted or rostrally dominant PrPSc distribution in the early stages.
  • PrPSc was detected in follicular dendritic cells of the spleen, lymph nodes, and Peyer's patch as early as 14-30 days post-inoculation, and in the thymus at 210 days.

Conclusions:

  • Intraperitoneal CJD infection leads to a diffuse CNS distribution of PrPSc, distinct from the pattern observed in intracerebral infections.
  • Peripheral lymphoid tissues, particularly spleen, lymph nodes, and Peyer's patch, serve as early sites for PrPSc accumulation following IP inoculation.
  • The thymus shows later involvement, with PrPSc detected in germinal centers of the medulla.

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