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Neuronal APP accumulates in toxic membrane blebbings
M Lesort1, F Terro, F Esclaire
1Neurobiology and Cellular Pathology Unit, ERS CNRS 6101, Laboratory of Histology and Cell Biology, Faculty of Medicine, Limoges, France.
Journal of Neural Transmission (Vienna, Austria : 1996)
|January 1, 1997
Summary
Mild excitotoxicity in neurons causes plasma membrane blebbing and amyloid precursor protein (APP) accumulation. These APP-rich blebs may be released, contributing to neurodegeneration in conditions like Alzheimer's disease.
Area of Science:
- Neuroscience
- Cell Biology
- Biochemistry
Background:
- Plasma membrane blebbing is an early cytotoxic event linked to cytoskeletal changes, poorly understood but potentially involving calcium (Ca2+) and free radicals.
- Amyloid precursor protein (APP) cleavage produces beta-amyloid (Abeta), a key component of Alzheimer's disease plaques.
Purpose of the Study:
- To investigate the effects of slow excitotoxicity on neuronal cytoskeleton and plasma membrane.
- To determine the role of amyloid precursor protein (APP) in excitotoxicity-induced blebbing.
Main Methods:
- Exposure of rat and human (hNT) neuronal cultures to NMDA.
- Immunocytochemical analysis using APP antibodies.
- Assessment of Ca2+-influx dependency using NMDA antagonists and Ca2+-depleted conditions.
Main Results:
- NMDA exposure induced cytoskeletal perturbations and plasma membrane blebbing in neurons.
- These blebs showed redistribution and accumulation of cellular APP.
- The phenomenon was dependent on Ca2+-influx via NMDA-receptors, inhibited by MK801 or low Ca2+.
Conclusions:
- Slow excitotoxicity in neurons is associated with APP-accumulating blebs.
- These blebs can be released extracellularly, suggesting a novel mechanism in neurodegeneration.
- Findings link APP processing and cellular blebbing in the context of excitotoxic neuronal injury.