Related Experiment Videos
Isolation and characterization of macrophages from scrapie-infected mouse brain
Abstract:
We have isolated and characterized a population of brain macrophages from normal and scrapie-infected mice. The cells are phagocytic, possess Fc-IgG receptors, Mac-1 surface antigen and proliferate in the presence of macrophage colony stimulating factor. They resemble microglia in that they have a plasmalemmal distribution of the enzyme nucleoside diphosphatase, a property tht is characteristic of microglia in situ. In two of the three combinations of scrapie agent and mouse strain examined, the number of brain macrophages was several fold higher than in normal control mice. The increase was not observed in mice infected intraperitoneally or in control mice inoculated with normal brain homogenate. The increase is detectable as early as 3-5 weeks postinoculation. The agent/host combination that failed to show an increase in brain macrophages is one that develops large numbers of amyloid plaques. These observations suggest that these cells are closely associated with the scrapie pathogenic process in the CNS. The failure of these cells to increase in the plaque forming model of scrapie disease also suggests that they play a role in the control of CNS amyloidogenesis.
Insights
Brain macrophages increase in scrapie infection, suggesting a role in disease pathogenesis. Their failure to proliferate in plaque-forming models indicates involvement in controlling central nervous system amyloidogenesis.
Area of Science:
- Neuroimmunology
- Neurobiology
- Infectious Diseases
Background:
- Scrapie is a transmissible spongiform encephalopathy affecting the central nervous system.
- Brain macrophages, including microglia, are key immune cells in the CNS.
- Understanding the role of these cells in neurodegenerative diseases is crucial.
Purpose of the Study:
- To isolate and characterize brain macrophages from normal and scrapie-infected mice.
- To investigate the proliferation and characteristics of these cells in response to scrapie infection.
- To determine the association of brain macrophages with scrapie pathogenesis and amyloid plaque formation.
Main Methods:
- Isolation and characterization of brain macrophages.
- Assessment of phagocytic activity, Fc-IgG receptors, and Mac-1 surface antigen.
- Evaluation of proliferation in response to macrophage colony stimulating factor.
- Analysis of cell numbers in normal and scrapie-infected mouse models.
Main Results:
- Isolated brain macrophages exhibit characteristics of microglia, including nucleoside diphosphatase distribution.
- Brain macrophage numbers significantly increased in two of three scrapie agent/mouse strain combinations.
- Increased cell numbers were observed early (3-5 weeks post-inoculation) and were specific to intracerebral scrapie infection.
- No increase in brain macrophages was seen in a plaque-forming scrapie model.
Conclusions:
- Brain macrophages are closely associated with the pathogenic process of scrapie in the CNS.
- The failure of brain macrophages to increase in plaque-forming models suggests a role in controlling CNS amyloidogenesis.
- These findings highlight the complex interplay between immune cells and neurodegeneration in prion diseases.