Related Experiment Videos
Reactive microglia/macrophages phagocytose amyloid precursor protein produced by neurons following neural damage
K Shigematsu1, P L McGeer, D G Walker
1Kinsmen Laboratory of Neurological Research, Department of Psychiatry, University of British Columbia, Vancouver, Canada.
Abstract:
Kainic acid lesions of rat striatum caused an elevation of amyloid precursor protein (APP) immunoreactivity in neurons and neurites, some of which were then phagocytosed by reactive microglia/macrophages. Immunoexpression of APP was observed in neurites and neurons 1 day after the kainic injection. Four days after lesioning, immunoreactivity was still concentrated in thick and distorted neurites, but it began to appear in microglia/macrophages and in the tissue matrix. The cells were identified as microglia/macrophages by the phenotypic markers Ia (OX6), leukocyte common antigen (OX1), C3bi receptor (OX42), and macrophage marker (ED1). They were negative for the astrocytic marker glial fibrillary acidic protein (GFAP). APP immunoreactivity in these phagocytic cells was most prominent between 1 week and 1 month postlesioning. No extracellular amyloid fibrils were detectable. These results suggest that APP production is rapidly upregulated in damaged neurons and accumulates in degenerating axons. However, phagocytosis of APP by reactive microglia/macrophages in this rat model does not result in production of Alzheimer type amyloid deposits.
Insights
Kainic acid lesions increase amyloid precursor protein (APP) in damaged neurons. Reactive microglia/macrophages engulf this APP, but do not form Alzheimer-type amyloid deposits in this rat model.
Area of Science:
- Neuroscience
- Cell Biology
- Pathology
Background:
- Amyloid precursor protein (APP) is implicated in neurodegenerative diseases.
- Understanding APP metabolism in neuronal injury is crucial.
Purpose of the Study:
- To investigate APP expression and processing in neurons and microglia following excitotoxic brain injury.
- To determine if APP phagocytosis by microglia leads to amyloid plaque formation.
Main Methods:
- Kainic acid-induced striatal lesions in rats.
- Immunohistochemical analysis of APP, microglial/macrophage markers (Ia, OX1, OX42, ED1), and astrocytic marker (GFAP).
Main Results:
- Kainic acid lesions elevated APP immunoreactivity in neurons and neurites.
- Reactive microglia/macrophages phagocytosed APP, with peak immunoreactivity observed 1 week to 1 month post-lesion.
- No extracellular amyloid fibrils were detected.
Conclusions:
- Neuronal APP production is upregulated following injury and accumulates in degenerating axons.
- Microglial phagocytosis of APP in this model does not result in Alzheimer-type amyloid deposition.