A Tau antisense oligonucleotide decreases neurone sensitivity to excitotoxic injury.

Abstract:

:Short-term exposure of primary cultures of cerebellar granule cells from neonatal rat brain to high concentrations of glutamate results in neuronal degeneration. We found that glutamate, before causing neuronal degeneration, induced a significant increase of Tau protein immunostaining. Time-course experiments revealed the increase ot Tau immunoreactivity to be maximal 2 h after the glutamate pulse. To investigate the possible role of newly synthesized Tau protein in the neurotoxic process activated by glutamate, cerebellar granule cells were preincubated with a specific Tau antisense oligonucleotide. This treatment resulted in (i) an inhibition of the glutamate-induced increase of Tau immunoreactivity and (ii) a decrease in the sensitivity of the neurones to neurotoxic concentrations of glutamate. These data indicate that new synthesis of the cytoskeleton-associated Tau protein is a crucial step in the cascade of events promoted by glutamate and leading to neurodegeneration.

journal_name

Neuroreport

journal_title

Neuroreport

authors

Pizzi M,Valerio A,Ribola M,Spano PF,Memo M

doi

10.1097/00001756-199306000-00057

subject

Has Abstract

pub_date

1993-06-01 00:00:00

pages

823-6

issue

6

eissn

0959-4965

issn

1473-558X

journal_volume

4

pub_type

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