Maintenance of the Innate Seizure Threshold by Cyclooxygenase-2 is Not Influenced by the Translational Silencer, T-cell Intracellular Antigen-1

Yifan Gong, James A. Hewett

Research output: Contribution to journalArticle

2 Scopus citations

Abstract

Activity of neuronal cyclooxygenase-2 (COX-2), a primary source of PG synthesis in the normal brain, is enhanced by excitatory neurotransmission and this is thought to be involved in seizure suppression. Results herein showing that the incidence of pentylenetetrazole (PTZ)-induced convulsions is suppressed in transgenic mice overexpressing COX-2 in neurons support this notion. T-cell intracellular antigen-1 (TIA-1) is an mRNA binding protein that is known to bind to COX-2 mRNA and repress its translation in non-neuronal cell types. An examination of the expression profile of TIA-1 protein in the normal brain indicated that it is expressed broadly by neurons, including those that express COX-2. However, whether TIA-1 regulates COX-2 protein levels in neurons is not known. The purpose of this study was to test the possibility that deletion of TIA-1 increases basal COX-2 expression in neurons and consequently raises the seizure threshold. Results demonstrate that neither the basal nor seizure-induced expression profiles of COX-2 were altered in mice lacking a functional TIA-1 gene suggesting that TIA-1 does not contribute to regulation of COX-2 protein expression in neurons. The acute PTZ-induced seizure threshold was also unchanged in mice lacking TIA-1 protein, indicating that this RNA binding protein does not influence the innate seizure threshold. Nevertheless, the results raise the possibility that the level of neuronal COX-2 expression may be a determinant of the innate seizure threshold and suggest that a better understanding of the regulation of COX-2 expression in the brain could provide new insight into the molecular mechanisms that suppress seizure induction.

Original languageEnglish (US)
Pages (from-to)37-51
Number of pages15
JournalNeuroscience
Volume373
DOIs
StatePublished - Mar 1 2018

Keywords

  • T-cell intracellular antigen-1
  • cyclooxygenase-2
  • gene expression
  • pentylenetetrazole
  • seizure threshold
  • seizures

ASJC Scopus subject areas

  • Neuroscience(all)

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