MODIFICATIONS OF NEURONAL PHOSPHORYLATED TAU IMMUNOREACTIVITY INDUCEDBY NMDA TOXICITY

Glutamate toxicity has been involved in the pathophysiology of a large variety of neurodegenerative disorders. tau Protein is a microtubule- associated protein that promotes microtubule polymerization and stabil ization. Phosphorylated tau protein accumulates in paired helical neur ofilaments, the major constituent of neurofibrillary tangles observed in the brain of patients suffering from Alzheimer disease (AD). In thi s study, using confocal laser microscopy and immunoblot analysis, we r eport that acute (500 mu M for 15 min) or chronic (20 mu M for 16 h) N -methyl-D-aspartate (NMDA) neuronal toxicities modify the immunoreacti vity of phosphorylated tau. Neuronal degeneration produced by N-methyl -D-aspartate is associated with an augmented immunolabeling of phospho rylated tau proteins at serine 202 (AT8 antibody) as observed in paire d helical neurofilaments. This finding could help to determine the cel lular mechanisms at the origin of neuronal degeneration associated wit h modifications of phosphorylated tau immunoreactivity produced by rec eptor-mediated extracellular signals.