GLUTAMATE TOXICITY ENHANCES TAU-GENE-EXPRESSION IN NEURONAL CULTURES

Tau protein is a microtubule-associated protein normally expressed in neurons, In Alzheimer's disease (AD) brains, phosphorylated tau accumu lates in paired helical filaments which form neurofibrillary tangles i n affected neurons; moreover, tau mRNA expression is increased in affe cted regions of AD brains, Glutamate, an excitatory neurotransmitter b ut also a potent neurotoxin under pathologic conditions, is known to p roduce neuronal degeneration and death accompanied by an increase in t au immunoreactivity ire primary neuronal cultures, The goal of the pre sent study is to evaluate the effects of glutamate on tau gene express ion in neuronal cultures, We report a delayed and long-lasting enhance ment of tau mRNA expression after a 15 min exposure to toxic concentra tions of glutamate: neuronal tau mRNA levels reach a peak after 3 hr a nd remain increased 6 and 12 hr after the end of glutamate exposure. B oth NMDA and AMPA/kainate receptors are involved in this tau gene over expression, Actinomycin D prevents this tau mRNA induction indicating that transduction signals ellicited by glutamate act at the transcript ional level, The role of this delayed tau overexpression is not elucid ed bat could be linked to either a reactive survival process or to a p rogrammed cellular degeneration, (C) 1997 Wiley-Liss, Inc.