Inhibition of glutamate-induced neurotoxicity by a tau antisense oligonucleotide in primary culture of rat cerebellar granule cells.
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.
Pizzi
M
M
Department of Biomedical Sciences and Biotechnologies, School of Medicine, University of Brescia, Italy.
Valerio
A
A
Arrighi
V
V
Galli
P
P
Belloni
M
M
Ribola
M
M
Alberici
A
A
Spano
P
P
Memo
M
M
D000818:Animals; D016375:Antisense Elements (Genetics) / Q000235:genetics; D001483:Base Sequence; D015153:Blotting, Western; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D002531:Cerebellum / Q000187:drug effects*; D018698:Glutamic Acid / Q000494:pharmacology*; D007425:Intracellular Membranes / Q000378:metabolism; D008969:Molecular Sequence Data; D009498:Neurotoxins / Q000037:antagonists & inhibitors* / Q000494:pharmacology*; D015345:Oligonucleotide Probes / Q000235:genetics; D016376:Oligonucleotides, Antisense / Q000494:pharmacology*; D009994:Osmolar Concentration; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D016875:tau Proteins / Q000235:genetics* / Q000378:metabolism
D016375:Antisense Elements (Genetics); D009498:Neurotoxins; D015345:Oligonucleotide Probes; D016376:Oligonucleotides, Antisense; D012333:RNA, Messenger; D016875:tau Proteins; D018698:Glutamic Acid; D002118:Calcium