The occurence of plasma membrane blebbings is an early cytotoxic event, associated with the reorganization of
cytoskeletal proteins, the alteration of interactions between the plasma membrane and the underlying cytoskeleton. The blebbing formation remains poorly understood but the involvement of cytosolic Ca2+ and the production of
free radicals may contribute to this cellular phenomenom. The
amyloid precursor
protein (APP), is a transmembrane
protein that can be cleaved to produce the
beta amyloid peptide (Abeta) which accumulates in brain
senile plaques of
Alzheimer's disease. Our study reveals that the exposure of rat and human (hNT) neuronal cultures to a mild concentration of the
excitotoxin NMDA slowly induces perturbations of the neuronal cytoskeleton and the occurence of plasma membrane blebbings. An immunocytochemical study using four different APP
antibodies demonstrates that these membrane
blebs are also associated with a redistribution and an accumulation of cellular APP. This phenomenon is linked to a Ca2+-influx through
NMDA-receptors since it is prevented by the
NMDA antagonist
MK801 or by Ca2+-depleted conditions. In conclusion this study shows that neuronal degeneration induced by slow excitotoxicity, is associated with the presence of APP-accumulating
blebs, that can be secondly released in the extracellular region.