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Inhibition of Glutamate‐induced Neurotoxicity by a Tau Antisense Oligonucleotide in Primary Culture of Rat Cerebellar Granule Cells
Author(s) -
Pizzi Marina,
Valerio Alessandra,
Arrighi Virginia,
Galli Paola,
Belloni Marco,
Ribola Marina,
Alberici Antonella,
Spano PierFranco,
Memo Maurizio
Publication year - 1995
Publication title -
european journal of neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.346
H-Index - 206
eISSN - 1460-9568
pISSN - 0953-816X
DOI - 10.1111/j.1460-9568.1995.tb01156.x
Subject(s) - glutamate receptor , neurotoxicity , neurodegeneration , tau protein , messenger rna , glutamic acid , microbiology and biotechnology , biology , chemistry , neuroscience , biochemistry , medicine , amino acid , toxicity , gene , alzheimer's disease , receptor , disease
Short‐term exposure of primary cultures of cerebellar granule cells from neonatal rat brain to high concentrations of glutamate resulted in a significant increase of both immunoreactivity to and mRNA levels of tau protein. Time‐course experiments revealed the increases of tau immunoreactivity and mRNA levels to be maximal 2 h after the glutamate pulse. To investigate the relationship between newly synthesized tau protein and glutamate‐induced neurotoxicity, neurons were preincubated with a specific tau antisense oligonucleotide. This treatment resulted in (i) inhibition of the glutamate‐induced increase of tau immunoreactivity and (ii) a decrease in the sensitivity of the neurons to neurotoxic concentrations of glutamate. These data indicate that induction of the cytoskeleton‐associated tau protein participates in the cascade of events promoted by glutamate leading to neurodegeneration.